bims-ecemfi 2026-10-04 papers

Adv Sci (Weinh). 2026 Sep 27. e77895

Nascent Extracellular Matrix Converts Biomaterial Cues into Cell Fate Decisions.

Joshua Y Liu, Ziqian Yang, Arina E Velieva, Eleanor M Plaster, Mingyue Fan, Donia W Ahmed, Avinava Roy, Pamela Duran, Pamela Panovich, Alexandra S Piotrowski-Daspit, Carlos A Aguilar, Megan L Killian, Claudia Loebel.

Hydrogels serve as powerful models for investigating cell-extracellular matrix (ECM) interactions. While chemical modifications are routinely used to tune hydrogel properties, it remains unclear whether these modifications mediate cell fate. Previous work has shown that cells deposit newly synthesized (nascent) ECM at the cell-hydrogel interface. Here, we demonstrate that this nascent ECM interface regulates how cells interpret chemical modifications. Using hydrogels with varied chemical modifications, we isolated the effects of chemical modification on nascent ECM and cell fate. Nascent ECM deposition increased as a function of hydrogel modification and with distinct matrisome compositions. While low-modification hydrogels promoted cell differentiation, high modifications increased cell proliferation. Perturbing cell- nascent ECM interactions reversed this cell fate. Our findings reveal that nascent ECM regulates cell fate by converting hydrogel cues into signals that control cell fate. This tri-directional interplay among hydrogel chemical modifications, nascent ECM, and cell fate reframes how we interpret cell-hydrogel interactions.

Keywords: biomaterial; cell biology; cell fate determination; cell growth; cellular differentiation; chemistry; extracellular matrix

DOI: https://doi.org/10.1002/advs.77895

Nat Commun. 2026 Aug 27. pii: 10266. [Epub ahead of print]17(1):

Lipid network crosslinked hydrogels control material dynamics across multiple length scales through lipid movement.

Neil J Baugh, Michelle S Huang, Narelli de Paiva Narciso, Jordan A Bunch, Jayniana Williams, Daiyao Zhang, Vanessa M Doulames, Yueming Liu, Ruby Onsongo, David Kilian, Renato S Navarro, Sarah C Heilshorn.

Control over network dynamics across length scales is a feature of natural materials challenging to replicate in synthetic hydrogels. Taking inspiration from biological materials that feature lipids as structural elements, we introduce Lipid Network Crosslinked (LINC) hydrogels that exploit the mobility of individual lipids within self-assembled liposomes as covalent, network-crosslinking points. These mobile, covalent crosslinks increase hydrogel stress relaxation rates over 20-fold compared to polymer-only hydrogels with equivalent stiffness. Liposome design parameters, including degree of surface functionalization and tail saturation, provide a means to independently control the macroscale storage moduli and stress relaxation behavior. Finally, we place cell-adhesive ligands onto more mobile or less mobile network elements. Human neural progenitor cells within LINC hydrogels significantly alter their phenotype in response to nanoscale ligand dynamics. These results establish LINC hydrogels as biomimetic materials that leverage nanoscale lipid mobility within a macroscale polymeric network to control dynamics at multiple length scales.

DOI: https://doi.org/10.1038/s41467-026-77268-8

Macromol Rapid Commun. 2026 Oct 02. e70444

Programming Stress Relaxation and Creep in Low-Molecular-Weight Self-Assembled Hydrogels Through Polymer Incorporation.

Ipsita Sahu, Kirti Nasir, Priyadarshi Chakraborty.

Mechanical property characterization of supramolecular viscoelastic materials, particularly low-molecular-weight gelator (LMWG)-derived hydrogels, has predominantly relied on small-amplitude oscillatory shear (SAOS) measurements, although these experiments probe network dynamics only at short timescales and fail to capture the full spectrum of network rearrangements that drive bulk mechanical behavior. A key challenge is unveiling how transient non-covalent interactions in LMWGs and covalent polymeric components collectively modulate viscoelasticity across multiple timescales. Herein, we investigate an LMWG-polymer hybrid hydrogel to demonstrate how the progressive integration of a covalent polymer into a self-assembled network regulates the bulk mechanical response, using short-timescale SAOS and long-timescale stress-relaxation and creep/creep-recovery experiments. Notably, frequency-sweep and stress-relaxation measurements reveal that the storage modulus and characteristic relaxation time exhibit distinct sensitivities to polymer concentration, with comparable stiffnesses occurring alongside noticeably different relaxation times in the intermediate polymer composition range. Creep/Creep-recovery measurements further show enhanced resistance to irreversible deformation and improved elastic recovery at low polymer loadings, whereas higher polymer concentrations primarily promote faster recovery dynamics through a transition from dual to single retardation behavior. These findings demonstrate that polymer incorporation can differentially modulate the stiffness and relaxation dynamics of LMWG-derived supramolecular networks, providing a framework for tuning viscoelastic behavior across multiple timescales.

Keywords: composite hydrogels; creep; dynamic mechanical analysis; materials science; polymer; stiffness; stress relaxation; supramolecular chemistry; supramolecular hydrogels; viscoelasticity

DOI: https://doi.org/10.1002/marc.70444

Cell Chem Biol. 2026 Sep 28. pii: S2451-9456(26)00327-2. [Epub ahead of print]

Curved adhesions resist disruption by high-affinity αv-integrin inhibitors.

Christina E Lee, Judith Martinez, Anna Amine, Wei Zhang, Chih-Hao Lu, Xingyuan Zhang, He You, Ching-Ting Tsai, Melissa L Nakamoto, Bianxiao Cui.

Integrins are transmembrane adhesion receptors and major therapeutic targets in cancer and fibrotic diseases. High-affinity αv-integrin inhibitors, including cilengitide and MK-0429, were developed to block integrin-dependent cell adhesions. These inhibitors have been shown to disrupt integrin-mediated focal adhesions on flat, ligand-coated surfaces. Here, we demonstrate that these inhibitors are ineffective against curved adhesions, a class of integrin-mediated adhesion structures that assemble in response to membrane curvature. We find that, unlike focal adhesions, curved adhesions form under low mechanical tension, rendering them resistant to these inhibitors that act by blocking force transmission. As a result, these inhibitors also do not prevent cancer cell invasion into soft, fibrous three-dimensional extracellular matrices, a process that depends on curved adhesions. These findings expose a limitation of current integrin-targeting strategies and may help explain why some inhibitors have underperformed in clinical trials.

Keywords: cancer biology; cell adhesions; cell migration; curved adhesions; focal adhesions; integrins; mechanobiology; membrane biophysics; membrane curvature; nanofabrication; small-molecule inhibitors

DOI: https://doi.org/10.1016/j.chembiol.2026.08.017

Adv Sci (Weinh). 2026 Sep 28. e77487

The Interplay of Curvature, Geometry, and Topology Shapes Tissue Organisation in Epithelial Shells.

Laura Morato, Jesús A Andrés-San Román, Juan Garrido-García, Carmen Gordillo-Vázquez, Ana M Palacios, Elisabeth Lidueña-Fernández, Katie McDole, Pedro Gómez-Gálvez, Valentina Annese, Luis M Escudero.

During morphogenesis, multicellular patterns emerge from coordinated processes at the single-cell level. This is characterised in flat epithelial layers, where average neighbour distributions follow conserved arrangements. However, less is known about how curvature defines tissue architecture. Epithelial shells constitute a critical structural stage in early mammalian embryonic development. Our analysis reveals how the closed, curved geometry of epithelial shells limits their 3D organisation. Here, we designed computational models that predict shell surface topology across different cell numbers. To validate the model, MDCK cysts with precise cell-level segmentation were analysed. Our results show that more pentagons are required to accommodate higher curvature per cell patch, a restriction also observed in early mouse embryos. Small cysts and embryos exhibited a restricted subset of polygon configurations, predominantly those maximising the area-to-perimeter ratio. We conclude that epithelial shells are organised under general rules mirroring other natural cages, revealing that geometric and curvature constraints guide early epithelial organisation.

Keywords: curvature; epithelial shells; tissue topology; voronoi diagrams

DOI: https://doi.org/10.1002/advs.77487