bims-enlima 2026-04-12 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2026–04–12
34 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Extracellular matrix chemistry tunes bacterial biofilm metabolism and optimizes fitness.
Tough and Rapidly Relaxing Hydrogels Via Programmable Crosslink Kinetics.
Bottom-Up Coacervate-Based Artificial Cells: Integrating Cellular Hallmarks into Complex Life-Like Systems.
Interface-governed electromechanical coupling in bioinspired hierarchical piezoelectric poly(L-lactide) architectures.
A Modular Platform for Effector Discovery in Induced-Proximity Lysine Acetylation.
Ultratough Organic-Inorganic Bicontinuous Network Hydrogel via Crosslinking Liquid-Like Inorganic Ionic Clusters With Polymer Chains.
Engineering Corynebacterium glutamicum as a multifunctional biofactory for living therapeutic materials and controlled ectoine delivery.
Integrating Biological Architecture and Biomaterial Function: Exploring the Native Hydrogel Structure of Brown Seaweed.
Millimeter-Scale Dual-Opposing RNA-Gradient Hydrogel for Interfacial Gene Silencing.
Selection-free whole genome transplantation revives dead microbes.
Impact of Process Interruptions in the Production of Lysates for Cell-Free Expression Systems.
Hydration-dependent mechanics and structural resilience of jelly fungi as natural blueprints for bioinspired hydrogels.
Advancing Bioink Homogeneity in Extrusion 3D Bioprinting with Active In Situ Magnetic Mixing.
Synergistic Hydrophobic and Hofmeister Effects Drive Recyclable, Tough, and Antiswelling Hydrogels for Underwater Communication.
Swelling-Tunable Hydrogels for Self-Transformable Underwater Flexible Electronics with Wireless Communication.
Dehydration-Induced Chain Entanglement for Tough, Low-Hysteresis, Double-Network Hydrogels.
Stable Protein-Based G-Quadruplex-Derived Supramolecular Bioinks as Tunable ECM-Mimetic Constructs Assembled by Combining Non-Covalent and Covalent Strategies.
CRISPR-Cas-based live cell imaging of genome dynamics.
BB-EIT: A Generalized Prediction Model for Protein Adsorption on Polymer Brushes Using Augmented Chemical Embeddings.
Designing aperiodic metamaterials using mechanical neural networks.
Synergistic Strategies in the Design of Dynamic Hydrogels: Lessons From the Hydrogen Bonding in the Nature.
A 3D-Printed Pulsatile Shear Stress Platform for Studying Endothelial Cell Mechanobiology.
Chemputer and chemputation-A universal chemical compound synthesis machine.
Uncovering cancer dependencies in peptide-interacting protein pockets.
Sequence Display enables large-scale sequence-activity datasets for rapid protein evolution.
Generative machine learning unlocks the first proteome-wide image of human cells.
Microbial hockey: bacteria can spin a 'puck' just by swimming.
Thermoreversible cell-derived extracellular matrix only hydrogel (CEOgel): Development, characterization, and applications.
LAML-Pro: Joint Maximum Likelihood Inference of Cell Genotypes and Cell Lineage Trees.
Epigenetic Control of Toehold-Mediated Strand Displacement for Programmable Molecular Circuit Regulation and Enhanced microRNA Detection.
Minimal life by computer.
The adaptive molecular landscape of reprogrammed telomeric sequences.
Programming Homogeneous Hydrogels Using Directional Ion Transport toward Rapid 3D Reconfiguration.
Synthetic budding morphogenesis by optogenetic receptor tyrosine kinase signaling.

Proc Natl Acad Sci U S A. 2026 Apr 14. 123(15): e2528666123

Extracellular matrix chemistry tunes bacterial biofilm metabolism and optimizes fitness.

Jinyang Li, Georgia R Squyres, Kathy Duong, Courtney Reichhardt, Matthew R Parsek, Dianne K Newman.

  Chemically complex extracellular matrices define cellular microenvironments and shape cell behavior across all domains of life. But how has evolution optimized these materials to ensure the success of multicellular communities? Inspired by the well-established composition-properties-function relationships in engineered materials, we hypothesized that analogous relationships exist in extracellular matrices, where the composition and interactions among various matrix components govern material properties and cellular physiology. Here, we examine Pseudomonas aeruginosa biofilms-representative of ubiquitous multicellular microbial assemblies in nature and disease. We show that electrostatic interactions between the cationic polysaccharide Pel and extracellular DNA (eDNA) compete with eDNA binding to pyocyanin (PYO), a diffusible redox-active metabolite that supports anaerobic metabolism via extracellular electron transfer (EET). From a materials perspective, biofilm-mimetic hydrogels and natural biofilms revealed that altering Pel's charge via pH adjustment or chemical acetylation, or tuning the Pel:eDNA ratio, directly and predictably modulates PYO retention and EET efficiency. Biologically, a lower Pel:eDNA ratio enhances biofilm metabolism under oxygen limitation, whereas a higher ratio promotes survival under antibiotic stress. Notably, these perturbations (pH, Pel structure, and abundance) can be achieved directly or indirectly through biological activities. Together, these findings highlight how biologically regulated matrix chemistry encodes tunable material properties that, in turn, affect cellular responses that confer biofilm fitness advantages. They further suggest cells might actively fine-tune the surrounding matrix chemistry to maximize survival across diverse environments. More broadly, our work establishes a materials-based framework for a mechanistic understanding of the biological functions of extracellular matrix components in multicellular communities.

Keywords:  biofilms; extracellular electron transfer; extracellular matrix; living materials; phenazines

DOI:  https://doi.org/10.1073/pnas.2528666123
Adv Mater. 2026 Apr 09. e23440

Tough and Rapidly Relaxing Hydrogels Via Programmable Crosslink Kinetics.

Yuanyuan Wei, Stephen J K O'Neill, Jade A McCune, Oren A Scherman.

  Replicating the synergy of high toughness and rapid stress relaxation found in native tissues remains a central challenge for synthetic hydrogels on account of their intrinsic mechanical-temporal trade-off. Here we introduce a supramolecular hydrogel platform that leverages kinetic programming to precisely regulate crosslink dynamics through molecular dissociation kinetics. This molecular design allows independent tuning of relaxation dynamics and fracture toughness, decoupling properties that are typically correlated. The resulting hydrogels exhibit stress relaxation ( t1/2${t}_{1/2}$ = 0.1-100 s) two orders of magnitude faster than conventional networks while achieving exceptional fracture energy ( Gc=14,500Jm-2$G_c = 14{,}500\,\mathrm{J\,m^{-2}}$ ), well above natural rubber. Slowing crosslink dissociation significantly enhances energy dissipation under load, revealing a kinetic principle for toughening viscoelastic networks. This work establishes a molecular blueprint for designing soft materials with programmable, time-dependent mechanics.

Keywords:  kinetic programming; programmable time‐dependent mechanics; stress relaxation dynamics; supramolecular hydrogels; toughness

DOI:  https://doi.org/10.1002/adma.202523440
Angew Chem Int Ed Engl. 2026 Apr 08. e00002

Bottom-Up Coacervate-Based Artificial Cells: Integrating Cellular Hallmarks into Complex Life-Like Systems.

Arjan Hazegh Nikroo, Angshuman Das, Madelief A M Verwiel, Jan C M van Hest.

  Living cells are remarkably sophisticated entities that form the basis of life. Bottom-up artificial cell research focuses on reconstructing their essential functions and behaviors in life-like compartments using synthetic and natural building blocks, which can advance our understanding of fundamental biological processes and drive technological and biomedical applications. In this review, we focus our discussion on recent developments in bottom-up artificial cell research with a particular emphasis on coacervate-based artificial cell systems that integrate multiple cellular hallmarks. We delineate how enhanced structural mimicry through organized compartmentalization affords improved control over function. We then examine how energy supply can be coupled to metabolic processes, growth, and adaptive responses in artificial cells. We also survey emerging systems that enable artificial cells to communicate with other artificial and living cells through responsive signaling and functional interactions. Finally, we present our vision on the opportunities and directions for artificial cell research moving forward.

Keywords:  artificial cells; artificial signaling; cell mimics; coacervates; synthetic cells

DOI:  https://doi.org/10.1002/anie.202600002
Mater Horiz. 2026 Apr 07.

Interface-governed electromechanical coupling in bioinspired hierarchical piezoelectric poly(L-lactide) architectures.

Martina Žabčić, Lea Gazvoda, Masoumeh Sepideh Salehidashtbayaz, Ita Junkar, Selestina Gorgieva, Andraž Rešetič, Matjaž Spreitzer, Marija Vukomanović.

Bioinspired materials frequently derive functionality from hierarchical organization and chemically active interfaces that mediate the conversion of mechanical stimuli into biological signals. Emulating such interface-governed mechanotransduction in synthetic soft matter remains a major challenge for electromechanical biomaterials. Here, we introduce a hierarchical piezoelectric polymer architecture in which plasma-engineered interfaces act as active functional elements that govern ultrasound-driven electromechanical coupling. Two piezoelectric poly(L-lactide) (PLLA) layers with distinct morphologies-a uniaxially drawn film and an electrospun fibrous mat-are directly bonded via plasma-assisted surface activation, enabling morphologically well-integrated and strong interfacial adhesion without additional adhesive phases. Under ultrasound excitation, mechanical energy is preferentially concentrated at the chemically activated interface, generating enhanced shear deformation and a synergistically amplified piezoelectric response that exceeds the performance of the individual layers. This interface-dominated electromechanical coupling translates efficiently to biological systems through an extracellular-matrix-mimetic fibrous surface, enabling effective transfer of electrically mediated cues to adherent cells. Ultrasound-activated piezostimulation of human keratinocytes demonstrates enhanced cell adhesion, proliferation, and cytoskeletal organization. By establishing chemically programmed interfaces as a new design axis for electromechanical energy transduction, this work defines a bioinspired materials chemistry paradigm for adaptive piezoelectric surfaces and interfaces with broad relevance to bioelectronics, regenerative medicine, and dynamic tissue engineering.

DOI: https://doi.org/10.1039/d6mh00147e
bioRxiv. 2026 Mar 13. pii: 2026.03.11.711209. [Epub ahead of print]

A Modular Platform for Effector Discovery in Induced-Proximity Lysine Acetylation.

Brianna Hill-Payne, Mohd Younis Bhat, George M Burslem.

The regulation of post-translational modifications (PTMs) is central to cellular biology and disease. Induced-proximity strategies enable manipulation of PTMs by recruiting modifying enzymes to proteins of interest, but identifying effective effector enzymes typically requires extensive heterobifunctional molecule synthesis before biological validation. Here we report a modular platform that enables rapid evaluation of PTM editing enzymes against defined protein substrates in living cells using compound-dependent or nanobody-mediated induced proximity. Using lysine acetylation as a model system, we demonstrate programmable acetylation of GFP, histone H3, and p53 through recruitment of diverse acetyltransferases. Effector identity dictates site-specific acetylation patterns, enabling selective PTM deposition across substrates and cellular compartments. This platform enables rapid identification of productive effector-substrate relationships prior to heterobifunctional molecule development, accelerating the design of induced-proximity chemical probes for targeted PTM editing.

DOI: https://doi.org/10.64898/2026.03.11.711209
Small. 2026 Apr 08. e73317

Ultratough Organic-Inorganic Bicontinuous Network Hydrogel via Crosslinking Liquid-Like Inorganic Ionic Clusters With Polymer Chains.

Yexuan Li, Yongjin Du, Manfang Hu, Lina Zhou, Junbo Gong, Yadong Yu.

  Mechanically robust hydrogels hold great promise in structural engineering and materials fields. However, high strength and high toughness are usually mutually exclusive, and simultaneously achieving both properties in a hydrogel remains challenging. Inspired by the structural design of double-network hydrogels and nano-reinforcement strategies, herein, we develop an ultratough hydrogel featuring an organic-inorganic bicontinuous network structure. Specifically, liquid-like calcium phosphate clusters (CPC) and polyvinyl alcohol (PVA) molecular chains are crosslinked at the ionic-molecular level to form an organic-inorganic bicontinuous network, which imparts the resulting PVA/CPC hydrogel with outstanding mechanical properties (tensile strength: 32.89 ± 4.67 MPa, toughness: 108.50 ± 19.27 MJ m- 3), surpassing those of most existing high-performance hydrogels. Furthermore, the PVA/CPC hydrogel demonstrates exceptional energy absorption and dissipation capabilities, enduring 100 000 cycles of stretching in water without fracture, thus exhibiting remarkable fatigue resistance. Damaged PVA/CPC hydrogel can be repaired via organic-inorganic re-crosslinking. These superior mechanical properties provide a solid foundation for the large-scale application of the PVA/CPC hydrogel in soft robotics, energy-absorbing cushioning materials. The proposed organic-inorganic crosslinking strategy, based on liquid-like inorganic ionic clusters and polymer chains, offers a promising approach for producing high-performance bicontinuous network structural materials.

Keywords:  fatigue resistance; liquid‐like inorganic ionic clusters; organic–inorganic bicontinuous networks; reparability; ultratough hydrogels

DOI:  https://doi.org/10.1002/smll.73317
Biomater Adv. 2026 Mar 30. pii: S2772-9508(26)00145-7. [Epub ahead of print]185 214847

Engineering Corynebacterium glutamicum as a multifunctional biofactory for living therapeutic materials and controlled ectoine delivery.

Berina Muhovic, Maria Puertas Bartolome, Lara Luana Teruel Enrico, Louise Dupont, Alain M Jonas, Karine Glinel, Aranzazu Del Campo, Christoph Wittmann.

  Living therapeutic materials (LTMs) are an emerging class of biomaterials that integrate living cells within engineered polymer matrices to provide dynamic and responsive functionalities. In this study, we engineered the robust, nonpathogenic, and GRAS-certified microorganism Corynebacterium glutamicum into a multifunctional biofactory for LTM applications. Using synthetic biology, we designed and constructed C. glutamicum strains capable of sensing, reporting, and producing the extremolyte ectoine. Ectoine is a clinically used compatible solute with cytoprotective and anti-inflammatory properties that is widely applied in dermatological formulations, nasal sprays, and ophthalmic preparations for the treatment of inflammatory and stress-related conditions. The engineered strains were further encapsulated in polymer-based living materials, including membrane-in-gel patches and core-shell hydrogel systems, to create skin-compatible and ocular-applicable therapeutic platforms. We developed genetic biosensors that detect diaminobutyric acid (DABA), a key intermediate in the ectoine biosynthesis pathway, to enable the time-resolved monitoring of cellular function. These biosensors, which are integrated with fluorescence and enzymatic reporter systems, allowed the noninvasive visualization of metabolic activity. Encapsulation strategies were optimized to ensure high metabolic activity, structural stability, and biocontainment, along with the controlled release of ectoine for potential applications in drug delivery and protective therapies. This work highlights the potential of C. glutamicum as a versatile platform for next-generation LTMs, offering precise monitoring and targeted therapeutic capabilities toward multifunctional living materials for precision medicine and environmental biosensing applications.

Keywords:  Biosensor; Corynebacterium glutamicum; Drug delivery; Ectoine; Encapsulation; Hydrogel; Living therapeutic material; Metabolic engineering; Precision medicine; Synthetic biology

DOI:  https://doi.org/10.1016/j.bioadv.2026.214847
Macromol Biosci. 2026 Apr;26(4): e00622

Integrating Biological Architecture and Biomaterial Function: Exploring the Native Hydrogel Structure of Brown Seaweed.

Linn Berglund, Richa Sharma.

  Brown seaweed is a naturally occurring composite that integrates alginate and cellulose within a hierarchical, hydrated architecture analogous to engineered hydrogel systems. This study hypothesizes that leveraging the native structure-function relationships of brown seaweed enables the development of functional hydrogel biomaterials while minimizing synthetic and chemical processing. Strategies are investigated to exploit the intrinsic biological structure and composition of brown seaweed blades across multiple formats, including native and purified blade structures, as well as fibrillated blades reassembled into hydrogels and foam structures via 3D printing and freeze-drying. The resulting biomaterials are characterized in terms of structure, hydrogel stability, and liquid absorption capacity in different media. The effects of purification are compared with those of native materials. In addition, porosity, mechanical, rheological, and cytocompatibility properties of the fibrillated and reassembled structures are evaluated. By preserving the natural architecture and avoiding extensive fractionation, this approach demonstrates the potential to create resource-efficient biomaterials with high liquid absorption (∼3600%), high porosity (∼93%), and shape-memory behavior after compression. Cytocompatibility reaches ∼73% viability at 50% extract but decreases to ∼59% at full concentration, indicating a concentration-dependent biological response, underscoring the need to balance minimal processing with biological performance for biomedical applications.

Keywords:  absorption; alginate; cytotoxicity; kelp; nanocellulose; structure

DOI:  https://doi.org/10.1002/mabi.202500622
Adv Sci (Weinh). 2026 Apr 07. e24144

Millimeter-Scale Dual-Opposing RNA-Gradient Hydrogel for Interfacial Gene Silencing.

Tyler Hoffman, Cong Truc Huynh, Marcus J Goudie, Peyton J Tebon, Hyojin Ko, Minh Khanh Nguyen, Kaelyn L Gasvoda, Yang Song, Kirsten Fetah, Ali Khademhosseini, Song Li, Eben Alsberg.

  Tissue interface restoration poses significant challenges in tissue engineering, particularly in areas requiring gradients of cellularity, biochemical composition, and mechanical properties essential for tissue-specific functions. Recent advancements in microfluidic technology have enabled the creation of hydrogels with spatially defined gradients of biological molecules for engineering gradient tissues that mimic the natural heterogeneity of the native extracellular matrix. However, these gradients are typically outside relevant millimeter length scales for biological interfaces. To address these challenges, a branched microfluidic system capable of generating millimeter-scale hydrogels with dual-opposing gradients of RNAi molecules nanocomplexed with thiolated polyethyleneimine is demonstrated. These nanocomplexes are incorporated into photocrosslinkable poly(ethylene glycol)-diacrylate (PEG-DA) monomer solutions, which are then injected and mixed within a PDMS microfluidic chip featuring a branched channel network. The process results in stable, linear, 3-mm dual-opposing RNA gradients within the hydrogel, which is subsequently photocrosslinked. The generated hydrogels demonstrate precise spatial regulation of gene expression within encapsulated cells, as confirmed by fluorescence analysis. This platform holds significant potential for engineering complex tissue constructs and enabling the targeted delivery of RNAi molecules, influencing both encapsulated and endogenous cells. This advancement could play a crucial role in the regeneration of critical tissue interfaces such as tendon-to-bone and cartilage-to-bone.

Keywords:  RNAi; biofabrication; gene silencing; gradient hydrogels; patterning; tissue engineering

DOI:  https://doi.org/10.1002/advs.202524144
bioRxiv. 2026 Mar 14. pii: 2026.03.13.711674. [Epub ahead of print]

Selection-free whole genome transplantation revives dead microbes.

Zumra Peksaglam Seidel, Nacyra Assad-Garcia, Vanya Paralanov, Feilun Wu, Olivia Chao, Elizabeth A Strychalski, Eugenia Romantseva, Tyler Goshia, J Craig Venter, John I Glass.

We present a living, synthetic bacterial cell made by transplanting a complete genome into a dead cell. After killing Mycoplasma capricolum cells by chemically crosslinking their genome with Mitomycin C (MMC), we installed synthetic Mycoplasma mycoides genomes into the resulting dead cells using Whole Genome Transplantation (WGT) 1,2 . During WGT, a synthetic donor genome is placed into a recipient cell, thereby reprogramming that cell to adopt a new genetic identity 3 . WGT has only been demonstrated using species within one phylogenetic clade of Mollicutes bacteria 4 . A major barrier to expanding WGT to diverse bacterial species has been the inability to inactivate the recipient genome, leading to false positive transplants due to homologous recombination of antibiotic resistance markers from the donor genome into the recipient cell genome. Here, we address this key limitation by removing reliance on an antibiotic resistance marker to select for transplants; recipient cells are dead unless revived by the installation of a new genome. Our work demonstrates a general approach to fully inactivate the recipient cell genome, reports the first living synthetic bacterial cell constructed from non-living parts, and advances WGT for building engineered or synthetic cells for diverse applications.

DOI: https://doi.org/10.64898/2026.03.13.711674
Biotechnol Bioeng. 2026 Apr 05.

Impact of Process Interruptions in the Production of Lysates for Cell-Free Expression Systems.

Katherine A Rhea, Ethan N Walters, Julie L Zacharko, Mia J Seergae, Thomas R Laws, Thomas C Maishman, Yun-Nam Choi, John T Lazar, Ashty Karim, Weston Kightlinger, Michael C Jewett, Matthew W Lux.

  Cell-free gene expression systems offer cell-like functionalities outside the confines of the cell, garnering increasing interest for applications from biomanufacturing to sensing. As applications expand, the need to implement economically scaled processes to produce cellular lysates grows. The protocols to produce these cellular lysates are complex, and the impact of altering many of the process variables remains understudied. Here, we set out to evaluate the effect of extended incubations at several points in the extract preparation process with the goal of identifying breakpoints that would enable flexibility in process implementation. As a model, we prepared lysates from 50 L cultures instead of typical 1 L volumes. We produced 72 lysates, 36 that were incubated overnight before and after culture centrifugation, and 36 that were incubated with and without a run-off reaction, each across different temperatures. We found that incubations before and after culture centrifugation substantially increased variability between culture replicates but did not reduce cell-free protein synthesis activity, contrary to conventional wisdom that materials should be kept cold as much as possible throughout the process. We also observed that omitting the run-off reaction reduced yields but resulted in lysates that were robust to incubation up to room temperature overnight. When a run-off reaction was included, activity dropped both as a function of duration and temperature, and the overall variability increased. Our work offers potential options for flexibility in implementing lysate production processes and motivates further investigation into how key processing steps relate to cell-free expression activity.

Keywords:  biomanufacturing; cell‐free expression; protein synthesis; scale‐up; synthetic biology

DOI:  https://doi.org/10.1002/bit.70199
Acta Biomater. 2026 Apr 03. pii: S1742-7061(26)00211-4. [Epub ahead of print]

Hydration-dependent mechanics and structural resilience of jelly fungi as natural blueprints for bioinspired hydrogels.

Soroosh Salehi, Christopher P Bivins, Debora Lyn Porter.

  Jelly fungi function as natural hydrogels capable of tolerating extreme hydration changes and large deformation, making them valuable models for resilient soft materials. This study examines the mechanical behavior of Exidia glandulosa and Phaeotremella frondosa across hydrated and dehydrated states using compression testing, nanoindentation, microscopy, and finite element modeling. The two species display distinct structure-property relationships governed by hyphal architecture. E. glandulosa contains thick, bundled hyphae and crystalline inclusions that support higher hydrated stiffness and strong recovery during cyclic loading. P. frondosa, with finer hyphae, behaves similarly to polymeric hydrogels but becomes exceptionally stiff when dried. These findings show that a reinforced hyphal network combined with a gel-rich matrix enables stability under repeated loading and offers design principles for synthetic hydrogels with improved mechanical resilience. STATEMENT OF SIGNIFICANCE: Hydrogels are inherently soft materials, and their mechanical performance is often limited by homogeneous network structures that deform uniformly underload. This study demonstrates that jelly fungi represent a natural class of soft hydrogels whose stiffness and resilience are enhanced not by chemical modification, but by the presence of embedded hyphal architecture within the gel matrix. These internal reinforcements enable jelly fungi to exhibit stiffness comparable to, and in some cases exceeding, that of polymeric hydrogels, while also providing improved resistance to large cyclic deformations. By revealing how structural design alone can tune mechanical behavior, this work highlights bioinspired strategies for engineering hydrogels with targeted stiffness, durability, and damage tolerance through architectural control rather than changes in material chemistry.

Keywords:  Bioinspired design; Hydrogels; Jelly fungi; Water-responsive materials

DOI:  https://doi.org/10.1016/j.actbio.2026.04.005
Device. 2026 Mar 20. pii: 101044. [Epub ahead of print]4(3):

Advancing Bioink Homogeneity in Extrusion 3D Bioprinting with Active In Situ Magnetic Mixing.

Ferdows Afghah, Sina Kheiri, Ava Ladd, Farrah Ye, Vera McCoy, Jane Bai, Sonika Kohli, Giovanni Zanderigo, Gabriela de Lima, Ritu Raman.

  Maintaining uniform cell and hydrogel distribution in extrusion 3D bioprinting is a critical challenge, especially for long-duration or high-throughput prints. We present a magnetically-actuated mixer (MagMix), a compact modular in situ platform that integrates into standard extrusion bioprinters to actively homogenize bioinks in real-time. MagMix utilizes an internal propeller driven by a servo-controlled external magnet, enabling continuous, active, tunable speed mixing without altering bioink formulation. Computational simulations and experimental validation enable optimizing propeller geometry and mixing parameters. We demonstrate the utility of MagMix across commonly used cellular bioinks with different viscosities to demonstrate that active in situ mixing prevents cell sedimentation, improves cell viability, and eliminates nozzle clogging over extended print sessions while preserving 3D print quality and cell differentiation capacity. MagMix can be readily integrated into any extrusion bioprinting workflow and offers a scalable, bioink-agnostic solution to improve reproducibility and functionality in bioprinted constructs for applications in tissue engineering.

Keywords:  3D Printing; Biofabrication; Bioink; Biomaterials; Bioprinting; Cell Sedimentation; Muscle Tissue Engineering; Tissue Engineering

DOI:  https://doi.org/10.1016/j.device.2025.101044
ACS Macro Lett. 2026 Apr 06.

Synergistic Hydrophobic and Hofmeister Effects Drive Recyclable, Tough, and Antiswelling Hydrogels for Underwater Communication.

Jupen Liu, Rongzheng Wang, Ting Li, Wei Lu, Huihui Tan, Qin Huang, Lin Tang, You Yu.

The development of high-performance hydrogels for underwater flexible electronics is hindered by a long-standing, seemingly irreconcilable trade-off among antiswelling capability, mechanical robustness, and recyclability. Here, we report a synergistic hydrophobic and Hofmeister effect (SHHE) strategy to fabricate recyclable, tough, and antiswelling hydrogels (RTASH). By incorporating salts (e.g., CO32-, SO42-) into a hydrophobically modified polymer network, RTASH achieves exceptional antiswelling performance (swelling ratio < 5% after 60 days), high toughness (fracture toughness: 1.9 MJ m-3), and stable ionic conductivity (0.35 S m-1). The dynamic physical cross-links enable full recyclability, with the material retaining over 80% of its mechanical strength after three reprocessing cycles. When applied as an underwater strain sensor, RTASH exhibits high sensitivity (GF = 0.6), fast response (0.3 s), and long-term stability over 60 days of continuous operation. Leveraging its tunable electromechanical properties, we demonstrate real-time Morse code communication underwater including the reliable transmission of SOS distress signals. This work presents a straightforward and sustainable material fabrication strategy to advance the development of environmentally adaptive underwater communication systems.

DOI: https://doi.org/10.1021/acsmacrolett.6c00140
ACS Appl Mater Interfaces. 2026 Apr 08.

Swelling-Tunable Hydrogels for Self-Transformable Underwater Flexible Electronics with Wireless Communication.

Guangqiu Yang, Xinyu Zhang, Jiahong Liu, Xin Wang, Yongqi Yang.

  Hydrogels have emerged as promising materials for flexible electronics due to their excellent biocompatibility, flexibility, and tunable physicochemical properties. However, traditional hydrogels often suffer from swelling-induced mechanical degradation, which limits their practical applications. In this study, a series of HEMA-HEA hydrogels were developed by modulating the ratio of hydroxyethyl methacrylate (HEMA) to hydroxyethyl acrylate (HEA). These hydrogels exhibited tunable antiswelling properties, optical transparency, mechanical robustness, and self-bonding capabilities. With increasing HEMA content, the hydrogels transitioned from hydrophilic to hydrophobic, significantly enhancing their mechanical performance and reducing swelling ratios. Notably, HEMA5-HEA0 demonstrated outstanding antiswelling behavior with a swelling ratio of only 0.9%, while HEMA4-HEA1 exhibited balanced mechanical properties and minimal strain hysteresis, making it an ideal candidate for flexible strain sensors. The fabricated sensors demonstrated sensitivity, excellent fatigue resistance, and stable operation underwater, enabling real-time motion sensing and wireless communication in aquatic environments. Additionally, by leveraging the self-bonding property and differential swelling behavior of HEMA-HEA hydrogels, we achieved postprogrammable transformation control, enabling the design of complex shapes and autonomous fixation of RFID chips underwater. The RFID embedded in the hydrogel could communicate normally underwater, indicating that the hydrogel had no effect on the transmission of wireless signals. This study provides new insights into the design of high-performance hydrogels and demonstrates their potential for flexible electronics and underwater applications.

Keywords:  antiswelling hydrogels; flexible electronics; liquid metal; underwater sensors; wearable devices

DOI:  https://doi.org/10.1021/acsami.6c04062
ACS Appl Mater Interfaces. 2026 Apr 08.

Dehydration-Induced Chain Entanglement for Tough, Low-Hysteresis, Double-Network Hydrogels.

Hongming Lu, Zixuan Yang, Jiayi Bai, Yixuan Ma, Xi Chen, Luke Yan.

  Highly entangled hydrogels achieve outstanding mechanical properties via dense physical entanglements as cross-links. However, their fabrication usually relies on processing concentrated precursor solutions, which limits their scalability and practical application. This study introduces a facile dehydration-induced entanglement approach to fabricating double-network hydrogels with programmable entanglement density. Initially, a single-network hydrogel is synthesized via UV polymerization of a precursor solution containing acrylamide (AAm), carboxymethyl chitosan (CMCS), cross-linkers, and a photoinitiator. Subsequent controlled dehydration of the hydrogel drives spontaneous polymer chain condensation, enabling dense intermolecular entanglements that are stabilized through secondary cross-linking of CMCS chains. The resulting hydrogel achieves a tensile strength of 798 kPa and a toughness of 1.98 × 103 J·m-2, representing 11-fold and 10-fold enhancements over conventional double-network hydrogels, respectively. These properties stem from the synergistic interplay of covalent networks and physical entanglements, that enables an optimal balance between high modulus and low hysteresis. This optimized stiffness-toughness profile renders the hydrogel an attractive candidate for applications in flexible electronics, advanced wound dressings, and controlled drug delivery systems. This methodology provides a robust platform for designing high-performance hydrogels without complex processing constraints.

Keywords:  chain entanglement; chitosan; double network hydrogel; low hysteresis; mechanical properties

DOI:  https://doi.org/10.1021/acsami.6c04377
Adv Mater. 2026 Apr 08. e21259

Stable Protein-Based G-Quadruplex-Derived Supramolecular Bioinks as Tunable ECM-Mimetic Constructs Assembled by Combining Non-Covalent and Covalent Strategies.

Vera Sousa, Rita Sobreiro-Almeida, Bart W L van den Bersselaar, E W Meijer, Ghislaine Vantomme, João Borges, João F Mano.

  G-quadruplex hydrogels hold great promise for biofabrication owing to their dynamic supramolecular nature, provided their inherent instability under physiological conditions is overcome. Here, a bioinspired strategy that synergistically combines supramolecular self-assembly, under macromolecular crowding conditions, with in-bath enzymatic covalent crosslinking was employed to create stable, protein-based G-quadruplex-derived hydrogels. Mimicking the crowded intracellular milieu, the addition of Ficoll enhances G-quadruplex stability and tunes the rheological behavior, while transglutaminase-mediated crosslinking reinforces the network, preserving its structural integrity over extended periods. This combined approach yields printable bioinks with optimal viscosity, yield stress, and shear-thinning properties, enabling the fabrication of complex, multilayered 3D constructs that support enhanced cell viability and proliferation within an extracellular matrix (ECM)-mimetic fibrillar environment. Moreover, the modulation of the crosslinking density allows controlling cellular responses, offering a versatile platform for tailoring the biomechanical microenvironment. This study establishes a new class of hybrid G-quadruplex hydrogel bioinks, exhibiting unprecedented stability under physiological conditions, biofunctionality, and off-the-shelf availability, unlocking their potential for advanced tissue engineering and regenerative medicine strategies.

Keywords:  3D bioprinting; G‐quadruplex hydrogels; covalent reinforcement; macromolecular crowding; supramolecular self‐assembly

DOI:  https://doi.org/10.1002/adma.202521259
Nat Rev Genet. 2026 Apr 08.

CRISPR-Cas-based live cell imaging of genome dynamics.

Yanyu Zhu, W E Moerner, Lei S Qi.

The 3D architecture and dynamics of the genome are crucial for regulation of genome stability, transcription and cellular function. CRISPR-based live imaging technologies have enabled real-time visualization of specific genomic loci and transcripts in living cells. These tools harness customized guide RNAs and nuclease-deactivated Cas effectors to achieve precise genomic targeting, and recent methodological advances provide the 3D spatiotemporal resolution required to decipher real-time chromatin communication. These methods are elucidating the biophysical properties of chromatin, linking dynamic enhancer-promoter interactions directly to transcription, and revealing the role of 3D genome dynamics in basic cellular processes and disease. Here, we summarize the development of CRISPR-based live-cell imaging techniques, highlight the complementary 3D microscopy and analysis methods compatible with these methods, and offer perspectives on their applications to uncover fundamental principles that govern genome dynamics and function.

DOI: https://doi.org/10.1038/s41576-026-00949-z
ACS Appl Mater Interfaces. 2026 Apr 06.

BB-EIT: A Generalized Prediction Model for Protein Adsorption on Polymer Brushes Using Augmented Chemical Embeddings.

Shiwei Su, Nobuyuki Tanaka, Yoshitaka Ushiku, Koichi Takahashi.

  Precise control of protein adsorption on polymer surfaces is essential in materials science and biomaterial design, with applications in antifouling materials, biosensors, cell culture, and drug delivery systems. However, the complex interactions between polymers and proteins and the limited availability of high-quality interaction data remain major challenges in polymer informatics. Current approaches often lack the generalizability needed to model diverse polymer-protein systems within a single unified framework, and there is a paucity of comprehensive predictive models capable of handling diverse polymer-protein interactions. To address these challenges, we introduce BB-EIT (Biointerface BERT Encoder for Interaction Translation), a novel generalized model designed to accurately predict the amount of diverse protein adsorption on polymer brushes. BB-EIT leverages the pretrained ChemBERTa large language model (LLM) architecture using SMILES strings for robust chemical representation and convenient data augmentation through SMILES enumeration. By adapting the pretrained model with an extended layer integrating a comprehensive set of physicochemical and biochemical features, including polymer thickness, water contact angle, and surface charge as well as protein isoelectric point (pI) and size, the BB-EIT showed state-of-the-art performance and strong generalizability. The model accurately predicted the adsorption behavior in previously unseen polymer and protein systems. This work represents an important step toward the data-driven design of biomaterials with tailored protein adsorption properties.

Keywords:  LLM; data augmentation; generalized model; machine learning; material informatics; polymer brush; protein adsorption

DOI:  https://doi.org/10.1021/acsami.5c25223
Mater Horiz. 2026 Apr 08.

Designing aperiodic metamaterials using mechanical neural networks.

Pietro Sainaghi, Zhidi Yang, Jonathan B Hopkins.

Designing aperiodic metamaterials that accurately achieve multiple behaviours is often not possible due to the enormity of the complex factors that need to be considered. Here we introduce a design approach that uses mechanical neural networks (MNNs) to determine the arrangement of different passive-beam designs within aperiodic metamaterials such that they achieve desired behaviours while considering all of realitity's factors. The MNNs physically learn how to arrange the passive beams by tuning the stiffness of their mechatronically controlled active beams using the same discrete states of stiffness as the passive beams until the desired behaviours are achieved. In this work, two aperiodic metamaterials that achieve different shape-morphing behaviours are designed using a MNN.

DOI: https://doi.org/10.1039/d6mh00089d
Macromol Rapid Commun. 2026 Apr 07. e70277

Synergistic Strategies in the Design of Dynamic Hydrogels: Lessons From the Hydrogen Bonding in the Nature.

Gege Wang, Xinzhen Fan, Chuanzhuang Zhao.

  Dynamic hydrogels face the challenge of balancing performance robustness with dynamic responsiveness, and traditional strategies often fail to address both. Inspired by the synergistic regulation of structure and function through multiple weak interactions in biological systems, this review examines how synergistic strategies centered on hydrogen bonding can resolve this contradiction. We explore how hydrogen bonds, with their short-range, directional, and reversible properties, form hierarchical synergistic networks with hydrophobic interactions, metal coordination, electrostatic interactions, and dipole interactions. Additionally, we emphasize the role of the solvent environment in coordinated regulation, revealing how ions, organic solvents, and small molecules indirectly modulate interpolymer hydrogen bonds by restructuring the hydrogen bond network of water or directly participating in competitive binding, thus governing the macroscopic performance of gels. Based on these synergistic principles, we describe their applications in realizing hydrogel functions such as high strength and toughness, impact resistance, adhesion, self-healing, actuation, shape memory, and luminescence. Finally, we provide an outlook on emerging frontiers, including data-driven design paradigms based on biological data mining and machine learning, as well as the integration of living cells to construct adaptive life-material hybrid systems for next-generation intelligent soft materials.

Keywords:  bio‐inspiration; hydrogels; hydrogen bonding; synergistic effect

DOI:  https://doi.org/10.1002/marc.70277
Anal Chem. 2026 Apr 08.

A 3D-Printed Pulsatile Shear Stress Platform for Studying Endothelial Cell Mechanobiology.

Valentin Romanov, Jinyuan Vero Li, Feihu Zhao, Delfine Cheng, Boris Martinac, Charles D Cox.

The tools for subjecting cells to high-magnitude shear stress within conventional cell culture dishes and well plates on an orbital shaking platform have remained unchanged for the past 30 years. Here, we develop a pipeline for creating custom cell culture dishes and well plates of arbitrary size and complexity using 3D printing technology. We describe two methods: direct 3D printing and reversible bonding of ACLAR film to 3D-printed structures. We show that the custom chambers support alignment of human aortic endothelial cells cultured under flow while capturing robust activation of extracellular signal-regulated kinase in a shear stress- and time-dependent manner. We show that shear stress regulates the post-translational modification of the shear-stress-sensitive mechanosensitive ion channel PIEZO1, resulting in an increase in N-linked glycosylation that may be relevant to the channel's ability to sense and respond to shear stress. We also developed the first scanning and transmission electron microscopy protocol compatible with cells mechanically stimulated on an orbital shaker and demonstrated another approach for customizing conventional labware. The simplicity of fabrication, cost-effectiveness of this pipeline, and the ability to process a large number of cells simultaneously for multiple downstream experimental end points mean that the methodology developed here is likely to be of broad utility in the in vitro study of endothelial mechanobiology.

DOI: https://doi.org/10.1021/acs.analchem.5c07456
Proc Natl Acad Sci U S A. 2026 Apr 14. 123(15): e2511080123

Chemputer and chemputation-A universal chemical compound synthesis machine.

Leroy Cronin, Sebastian Pagel, Abhishek Sharma.

  Chemputation treats chemical synthesis as the execution of reaction code on programmable hardware. We show that a Chemputer, equipped with an extensible set of reagents, catalysts, and process conditions, together with a compiler that maps reaction and hardware graphs, is universal. This means it can produce any stable, isolable molecule in finite time and detectable quantity, provided real-time error correction maintains sufficient step fidelity relative to the number of steps in the synthesis. We formalize this into a Chemical Synthesis Turing Machine (CSTM), which defines chemical execution through a unified description of reagents, process variables, and catalysts. The framework introduces the Universal Chemputation Principle and a dynamic error-correction scheme that enables fault-tolerant synthesis. Linking this framework to assembly theory strengthens the definition of a molecule by demanding practical synthesizability and error correction becomes a prerequisite for universality. We demonstrate the abstraction is universal with more than 100 χDL programs executed on modular Chemputers, from single-step reactions to multistep syntheses. In each case, the number of unit operations scales linearly with synthetic depth. These results establish programmable chemical synthesis, chemputation, as a subset of general computation where χDL programs are compiled to hardware, executed with closed-loop control, and yield verifiable molecular outputs. This formalization enables shareable chemical code, interoperable hardware, and a machine-verifiable, executable foundation for a searchable and formally provable map of chemical space.

Keywords:  chemical synthesis; chemputation; chemputer; computer science; universality

DOI:  https://doi.org/10.1073/pnas.2511080123
bioRxiv. 2026 Mar 15. pii: 2026.03.13.711608. [Epub ahead of print]

Uncovering cancer dependencies in peptide-interacting protein pockets.

Mihkel Örd, Liz Kogan, Devin Bradburn, Michelle Leiser, Mardo Kõivomägi, Norman E Davey, Pau Creixell.

Cancer cells often become dependent on specific molecular functions. As many proteins perform multiple functions mediated by different pockets and interfaces, we hypothesized that we could identify distinct cancer dependencies and therapeutic vulnerabilities by disrupting peptide-binding pockets. To test this hypothesis, we screened a proteome-wide library of 7152 genetically encoded peptides across nine cancer cell lines. We identify common and selective dependencies on peptide-binding pockets and find that gene knockout and peptide-mediated inhibition of pockets often drive divergent phenotypes. For the common-essential gene HCF1, we identify a therapeutic window by using inhibitory peptides with varying affinity. Moreover, peptides targeting TLE1-4 reveal a dependency hidden in genetic screens by homolog redundancy. We also uncover that peptides inhibiting cyclin D drive specific suppression of leukemia cell proliferation and demonstrate that these peptides improve the potency of CDK4/6 inhibitors. Overall, our screening platform facilitates data-driven prioritization of molecular pockets for subsequent therapeutic translation.

DOI: https://doi.org/10.64898/2026.03.13.711608
Nat Biotechnol. 2026 Apr 08.

Sequence Display enables large-scale sequence-activity datasets for rapid protein evolution.

Linqi Cheng, Xinzhe Zheng, Shiyu Jason Jiang, Yu Hu, Yijie Liu, Kaiqiang Yang, Jinyan Rui, Haoxue Ding, Mengxi Zhang, Teng Yuan, Qianglan Lu, Haoxin Ye, Chen-Long Li, Yiming Guo, Zuotong Tian, Anna Qin, Boyang Zhou, Kevin K Yang, Xiongyi Huang, Han Xiao.

Engineering proteins with desired functions remains challenging and usually requires multiple rounds of screening and selection. Here, we present Sequence Display, a platform that generates large-scale protein sequence-activity datasets in a single round. Sequence Display enables multiplexed assessment of individual variant activity within a single experiment, offering a robust approach to mapping detailed sequence-function relationships. We demonstrate the platform's broad applicability by generating datasets for cytosine deaminase, uracil glycosylase inhibitor, aminoacyl-tRNA synthetase and a compact Cas9 nuclease. Integrating these datasets obtained from Sequence Display with pretrained protein language models, fine-grained, variant-specific activity landscapes can be constructed. We discovered several Cas9 variants with expanded protospacer-adjacent motif recognition and evolved aminoacyl-tRNA synthetase variants capable of recognizing different noncanonical amino acids. Together, this study establishes Sequence Display as a powerful tool for mapping protein activity landscapes and accelerating the discovery of optimized proteins for biological and medical applications.

DOI: https://doi.org/10.1038/s41587-026-03087-3
bioRxiv. 2026 Apr 02. pii: 2026.03.31.715748. [Epub ahead of print]

Generative machine learning unlocks the first proteome-wide image of human cells.

Huangqingbo Sun, Konstantin Kahnert, Jan N Hansen, William Leineweber, Mingyang Li, Wanyue Feng, Frederic Ballllosera, Ulrika Axelsson, Wei Ouyang, Emma Lundberg.

The spatial organization of proteins within cells governs virtually all cellular functions. Yet, current imaging technologies can simultaneously visualize only tens of proteins, orders of magnitude below the thousands that populate a single human cell. Here, we present ProtiCelli , a deep generative model that simulates microscopy images for 12,800 human proteins from just three cellular landmark stains. Trained on 1.23 million images from the Human Protein Atlas, ProtiCelli outperforms existing methods in reconstruction accuracy and textural fidelity, and generalizes to unseen cell types and drug perturbations absent from training. We demonstrate that ProtiCelli -generated images preserve hierarchical subcellular organization, recapitulate known protein-protein interaction landscapes, and resolve compartment-specific functions of moonlighting proteins at the single-cell level. Remarkably, the model infers drug-induced changes in protein expression and localization from cell morphology alone, predicts cell cycle stage without dedicated cell cycle markers, and enables unsupervised segmentation of subcellular compartments as well as spatial decomposition of gene sets into functional regions. Ultimately, we leverage ProtiCelli to generate Proteome2Cell , an unprecedented dataset of 30.7 million simulated images creating 2,400 "virtual cells" across 12 human cell lines. These proteome-scale images enable the construction of hierarchical single-cell models that distinguish conserved from dynamic protein architectures. Integration of Proteome2Cell into the Human Protein Atlas democratizes the exploration of these "virtual cells". By computationally bridging the experimental scalability gap, ProtiCelli establishes a foundation for spatial virtual cell modeling and paves an avenue for transforming spatial proteomics from cataloging proteins to simulating complete cellular systems.

DOI: https://doi.org/10.64898/2026.03.31.715748
Nature. 2026 Apr 09.

Microbial hockey: bacteria can spin a 'puck' just by swimming.



Keywords:  Biophysics

DOI:  https://doi.org/10.1038/d41586-026-01112-8
Mater Today Bio. 2026 Jun;38 103040

Thermoreversible cell-derived extracellular matrix only hydrogel (CEOgel): Development, characterization, and applications.

Byoungha An, Jae Won Kwon, Heejeong Yoon, Tae-Eun Park, Seung Won Yang, Kwideok Park.

  Decellularized extracellular matrix (dECM) has been widely used as a biomimetic material for three-dimensional cell culture and tissue regeneration. Although tissue-derived ECM is the conventional source of dECM, cell-derived ECM (cECM) has emerged as an attractive alternative. Various cECM-based formulations such as powders, films, and preformed gels have been reported, but thermosensitive cECM hydrogels remain largely unexplored. Here, we report a novel method to produce a thermoreversible hydrogel exclusively made from cECM, termed CEOgel. Once in vitro-cultured umbilical cord mesenchymal stem cells were decellularized, cECM solubility was enhanced and its nanofibers were concentrated to generate CEOgel without additional factors. This fabrication strategy was applicable across multiple cell types and consistently yielded homogeneous gels with minimal donor- or batch-dependent variability. CEOgel exhibited sufficient mechanical stability for in vitro use and formed gels in vivo following injection, confirming its thermosensitive and biocompatible nature. It also served as a functional 3D matrix, supporting endothelial vascularization in microfluidic chips and the growth of colorectal cancer organoids. Proteomic profiling revealed that CEOgel incorporates a broad spectrum of proteins commonly expressed across human tissues. Additionally, we demonstrated that CEOgel properties can be tuned through transition-metal crosslinking and genetically engineering ECM-producing cells. Together, this study proposes a new class of thermoreversible cECM hydrogels that eliminate reliance on animal tissues or external cross-linkers while expanding the applicability of cECM materials and advancing conceptual diversity for ECM hydrogel design. Our findings highlight the potential of CEOgel as a regenerative biomaterial for tissue engineering and medical applications.

Keywords:  Cell-derived extracellular matrix; Decellularized extracellular matrix; ECM hydrogel; Thermoreversible; Thermosensitive

DOI:  https://doi.org/10.1016/j.mtbio.2026.103040
bioRxiv. 2026 Mar 31. pii: 2026.03.27.714879. [Epub ahead of print]

LAML-Pro: Joint Maximum Likelihood Inference of Cell Genotypes and Cell Lineage Trees.

Gillian Chu, Henri Schmidt, Benjamin J Raphael.

Motivation: Recent dynamic lineage tracing technologies use genome editing to induce heritable mutations, or edits, that accumulate across successive cell divisions. These edits are measured using single-cell sequencing or imaging, providing data to reconstruct cell lineages at single-cell resolution. Current computational approaches to infer cell lineage trees, or phylogenies, from these data perform two separate steps: (1) Identify each cell's edits (genotype) from the raw sequencing or imaging data; (2) Infer a cell lineage tree from the cell genotypes. However, genotyping cells is an inexact process and genotype errors can yield an inaccurate lineage tree. For example, using fluorescence based-imaging to measure edits results in a high fraction (≈ 25-50%) of uncertain or erroneous genotypes.
Results: We introduce Lineage Analysis via Maximum Likelihood with PRobabilistic Observations (LAML-Pro), an algorithm that jointly infers cell genotypes and a cell lineage tree. LAML-Pro is based on the Probabilistic Mixed-type Missing Observation (PMMO) model, which we derive to describe both the genome editing and genotype observation processes. LAML-Pro constructs lineage trees from thousands of cells in under an hour by leveraging the sparsity of transitions under the PMMO model. On simulated data, we demonstrate that LAML-Pro corrects genotype errors and infers substantially more accurate trees than existing methods which are vulnerable to genotype errors. Applied to data from two recent imaging-based lineage tracing systems, LAML-Pro reduces genotype errors by 5-fold and produces more spatially coherent lineage trees compared to existing methods.
Availability and Implementation: LAML-Pro is freely available at: github.com/raphael-group/LAML-Pro .

DOI: https://doi.org/10.64898/2026.03.27.714879
ACS Nano. 2026 Apr 08.

Epigenetic Control of Toehold-Mediated Strand Displacement for Programmable Molecular Circuit Regulation and Enhanced microRNA Detection.

Yuxuan Zhu, Chongyu Xie, Hui Wang, Jinhua Shang, Xiaoqing Liu, Fuan Wang.

  Conventional toehold-mediated strand displacement─a cornerstone of dynamic DNA nanotechnology─is fundamentally limited by its reliance on the fixed toehold stability to control reaction kinetics, restricting precise and reversible regulation of molecular circuits. Here, we describe an epigenetically regulated system that exploits single-nucleobase N6-methyladenosine (m6A) modification within the toehold domain to achieve programmable kinetic control over DNA strand displacement. Site-specific m6A methylation disrupts base pairing at the toehold domain, effectively inhibiting strand displacement rates. This inhibition is precisely and reversibly modulated by demethylase FTO, which removes m6A modifications and restores toehold reactivity. Applied to catalytic hairpin assembly, this strategy not only enables the controlled inhibition and restoration of nucleic acid circuit function but also enhances its sensitivity and specificity in microRNA detection, exemplified by the intracellular imaging of cancer-associated microRNA-21. Our combined theoretical and experimental analyses indicate that both the location and density of m6A modifications critically dictate the extent of reaction inhibition, supporting the use of single-base epigenetic modifications as a versatile tool for chemical system design. This epigenetically regulated platform provides a general framework for dynamic nucleic acid circuits, with broad implications for biosensing, molecular computing, and synthetic biology, advancing the development of epigenetically controlled biochemical systems.

Keywords:  DNA methylation; fluorescence; imaging; microRNA; strand displacement

DOI:  https://doi.org/10.1021/acsnano.6c01658
Nat Biotechnol. 2026 Apr 07.

Minimal life by computer.

DOI: https://doi.org/10.1038/s41587-026-03110-7
Nat Commun. 2026 Apr 09.

The adaptive molecular landscape of reprogrammed telomeric sequences.

Melania D'Angiolo, Benjamin P Barré, Sakshi Khaiwal, Julia Muenzner, Johan Hallin, Matteo De Chiara, Nicolò Tellini, Jonas Warringer, Markus Ralser, Eric Gilson, Gianni Liti.

Telomeric sequences vary across the tree of life and intimately co-evolve with telomere-binding protein complexes. However, the molecular mechanisms allowing organisms to adapt to new telomeric sequences are difficult to gauge from extant species. Here, we engineer multiple yeast lines to human-like telomeric repeats to unveil their molecular and fitness response to reprogrammed telomeres. Initially, the exchange of telomere sequences results in genome instability, proteome remodelling and severe fitness decline. Adaptive evolution experiments select for repeated mutations that drive adaptation to the humanized telomeres. These consist of the recurrent amplification of the telomere-binding protein gene TBF1, by complex aneuploidies, or in repeated mutations that attenuate the DNA damage response. Overall, our results outline a response that defines the adaptive molecular landscape to reprogrammed telomeric sequences.

DOI: https://doi.org/10.1038/s41467-026-71475-z
ACS Nano. 2026 Apr 09.

Programming Homogeneous Hydrogels Using Directional Ion Transport toward Rapid 3D Reconfiguration.

Shiya Qiao, Xiaoxia Le, Tao Chen, Jingling Yan, Zhen Wang.

  Environmentally adaptive hydrogels undergo reconfiguration under external stimuli, suitable for intelligent sensing, bioinspired actuation, and soft robotics. However, achieving programmable three-dimensional (3D) morphing in homogeneous hydrogels under constant stimuli remains quite challenging despite the tremendous research efforts. Herein, inspired by the directional ion-transport actuation of starfish, supramolecular poly(amic acid) salt (PAAS) hydrogels with predictable 3D structure formation were developed through directional metal ion transport imparted by seawater. These hydrogels were prepared through aqueous polymerization of 3,3',4,4'-biphenyltetracarboxylic dianhydride (s-BPDA) and p-phenylenediamine (PDA) in the presence of organic bases with imidazole moieties (1,2-dimethylimidazole (DMZ), imidazole (IM), and 1-(2-hydroxyethyl)imidazole (HIM)), followed by thermal treatment at 50 °C. The resultant hydrogels, featuring high-density carboxylates, enable programmable 3D shape-morphing under seawater stimulation through spatially asymmetric (Ca2+/Mg2+)-carboxylate cross-linking and swelling/contraction. The dynamic supramolecular networks provide remarkable reconfigurability, with repeated reconstruction of complex 3D architectures. Specifically, the hydrogels show exceptional stability with low equilibrium swelling ratios (<50%), increased tensile strength (up to 2.1 MPa), and all 180° deformations completed within 70 s. Overall, programming 3D morphologies of homogeneous hydrogels using a single stimulus has potential for advancing shape-morphing engineering.

Keywords:  ion cross-linking; poly(amic acid) salt; polyelectrolyte hydrogel; programmable morphing; seawater response

DOI:  https://doi.org/10.1021/acsnano.5c19580
bioRxiv. 2026 Apr 02. pii: 2026.03.31.715459. [Epub ahead of print]

Synthetic budding morphogenesis by optogenetic receptor tyrosine kinase signaling.

Louis S Prahl, Ronald Canlla, Aria Zheyuan Huang, Daniel S Alber, Sandra L Shefter, Sachin N Davis, Samuel H Grindel, Zikang Dennis Huang, Thomas R Mumford, William Benman, Lukasz J Bugaj, Kyle W McCracken, Alex J Hughes.

The mammalian kidney relies on a branched network of collecting ducts for fluid transport and homeostasis. Replicating this network in vitro would parallelize function in synthetic replacement kidneys, yet current organoids have limited branching capacity. Here, we establish a developmentally-informed strategy to control organoid budding through optogenetic control of a receptor tyrosine kinase, RET. We first show pharmacological manipulation of RET signaling controls the extent of branching in mouse embryonic kidneys and human stem cell-derived kidney organoids. Next, we develop an optogenetic RET receptor (optoRET) that signals in a ligand-independent manner via blue light-mediated clustering. Epithelial cells expressing optoRET reproduce stereotyped RET signaling, scattering, and symmetry breaking in response to blue light. Human kidney organoids undergo budding with controllable orientation in response to spatially patterned optoRET stimulation. Our results establish ligand-free optogenetic control of branching and inspire new synthetic biology strategies for epithelial organoid design.
Highlights: GDNF-RET controls branching and tip cell state in mouse and human kidney tissues.OptoRET reproduces endogenous RET signaling and morphogenesis in cell lines.OptoRET enables ligand-free budding in human renal epithelial organoids.Spatially patterned optoRET stimulation controls budding orientation.

DOI: https://doi.org/10.64898/2026.03.31.715459