bims-ceblev Biomed News
on Cell mechanics, blebs, and extracellular vesicles
Issue of 2026–02–08
nine papers selected by
Juan Manuel García Arcos, École Polytechnique Fédérale de Lausanne
  1. ADAMTS proteases in extracellular vesicles: emerging mediators of extracellular matrix dynamics and disease progression.
  2. Interplay between cortical adhesion and membrane bending regulates the formation of microparticles.
  3. Chemical Biology Tools for Decoding the Cell Surface GlycoRNA.
  4. From biting to engulfment: curvature-actin coupling controls phagocytosis of soft, deformable targets.
  5. CaMKII nucleates an osmotic protein supercomplex to induce cellular bleb expansion.
  6. A role for PaxB in regulating blebbing: experimental insights and theoretical perspectives from Dictyostelium discoideum.
  7. Tissue-Specific Extracellular Vesicles Enriched From Circulation: Exploring the Liquid Biopsy Perspective.
  8. Chemotherapy-induced transfer of apoptotic machinery in extracellular vesicles between somatic and germ cells of the testis: mechanistic insights into onco-fertility preservation in pre-pubertal boys.
  9. Septins buffer actomyosin forces to protect the nucleus from genotoxic mechanical stress.
  1. FEBS J. 2026 Feb 03.
    ADAMTS proteases in extracellular vesicles: emerging mediators of extracellular matrix dynamics and disease progression.
    Carlos Peris-Torres, Juan Carlos Rodríguez-Manzaneque.
      Recent advances highlight extracellular vesicles (EVs) as key mediators of intercellular communication, carrying a complex cargo that includes extracellular matrix (ECM) components and associated modulators. Among them, ADAMTS proteases are emerging as pivotal regulators due to their ability to orchestrate precise ECM remodeling events and influence cellular behavior in pathological contexts such as cancer, vascular diseases, and tissue regeneration. Notably, the identification of specific ADAMTS family members within EV populations suggests that EVs may serve as vehicles for paracrine delivery and localized proteolytic activity, enabling spatially and temporally restricted ECM modulation. This review synthesizes current knowledge on the association between EVs and ADAMTS proteases, including their known substrates, and highlights their converging roles in shaping the extracellular landscape. We also discuss key knowledge gaps, especially concerning the diversity of ADAMTS-EV interactions, their functional impact in different physiological and pathological settings, and some reflections regarding their potential translational opportunities.
    Keywords:  ADAMTS proteases; EV corona; extracellular matrix; extracellular vesicles; inflammation; intercellular communication
    DOI:  https://doi.org/10.1111/febs.70433
  2. Soft Matter. 2026 Feb 03.
    Interplay between cortical adhesion and membrane bending regulates the formation of microparticles.
    Arijit Mahapatra, Sage A Malingen, Padmini Rangamani.
      Cells release vesicles that serve important roles in long-range signaling and intercellular communication. These vesicles are released not just in response to stress, inflammation, injury, and chemoresistance, but also during homeostatic regulation. A particular class of vesicles called ectosomes or microparticles are released by the outward budding of the plasma membrane, a process which requires both the detachment of the membrane from the cortex and the exposure of negatively charged, curvature-inducing lipids such as phosphatidylserine from the inner leaflet to the outer leaflet. In this work, we develop a biophysical model that accounts for the interaction between these different factors. Using our model, we predict how linker properties influence outward budding of the plasma membrane and identify conditions that can promote or inhibit membrane curvature generation. These findings provide insight into the fundamental mechanisms underlying microparticle formation, elucidating the basic biology of this critical process. Further, these mechanistic insights may inspire techniques for inhibiting microparticles where they are harmful, such as chemoresistant drug efflux by tumor cells.
    DOI:  https://doi.org/10.1039/d5sm01237f
  3. Angew Chem Int Ed Engl. 2026 Feb 05. e26098
    Chemical Biology Tools for Decoding the Cell Surface GlycoRNA.
    Xinming Zhang, Yingying Zhu, Xiangli Shao, Haoyue Dong, Michiel Noe, Yuan Ma.
      The discovery of glycosylated RNAs (glycoRNAs) on the outer surface of mammalian cells, represents a spatial awakening in RNA biology. This identification redefines the spatial boundaries of RNA biology, possibly extending its role beyond the nucleus and cytoplasm to the extracellular membrane interface. This unexpected localization and the presence of glycosylation modifications challenge longstanding conventional paradigms and raise new questions about the biosynthetic pathways, structural diversity, and signaling functions of glycoRNAs in the intercellular environment. Chemical biology tools are central to their discovery, further identification, and future exploration, enabling enrichment, imaging, and functional analysis of glycoRNAs in both physiological and pathological contexts. In this review, we highlight how these technologies have driven the discovery of glycoRNAs and revealed new principles of RNA localization and membrane-related functions. We further discuss several challenges and future directions in decoding the RNA-centric membrane biology.
    Keywords:  RNA; cell surface RNA; chemical biology; glycosylation
    DOI:  https://doi.org/10.1002/anie.202526098
  4. ArXiv. 2026 Jan 28. pii: arXiv:2601.20719v1. [Epub ahead of print]
    From biting to engulfment: curvature-actin coupling controls phagocytosis of soft, deformable targets.
    Shubhadeep Sadhukhan, Caitlin E Cornell, Mansehaj Kaur Sandhu, Youri Peeters, Samo Penič, Aleš Iglič, Daniel A Fletcher, Valentin Jaumouillé, Daan Vorselen, Nir S Gov.
      Phagocytosis is a fundamental process of the innate immune system, yet the physical determinants that govern the engulfment of soft, deformable targets remain poorly understood. Existing theoretical models typically approximate targets as rigid particles, overlooking the fact that both immune cells and many biological targets undergo significant membrane deformation during contact. Here, we develop a Monte Carlo-based membrane simulation framework to model the interactions of multiple vesicles, enabling us to explore phagocytosis-like processes in systems where both the phagocyte and the target possess flexible, thermally fluctuating membranes. We first validate our approach against established observations for the engulfment of rigid objects. We then investigate how the mechanical properties of a soft target -- specifically membrane bending rigidity govern the outcome of phagocytic interactions. Our simulations reveal three distinct mechanical regimes: (i) biting or trogocytosis, in which the phagocyte extracts a portion of the target vesicle; (ii) pushing, where the target is displaced rather than engulfed; and (iii) full engulfment, in which the target is completely internalized. Increasing membrane tension via internal pressure produces analogous transitions, demonstrating a unified mechanical origin for these behaviours. Qualitative comparison with experiments involving Giant Unilamellar Vesicles (GUVs, deformable microparticles) and lymphoma cells supports the relevance of these regimes to biological phagocytosis. Together, these results highlight how target deformability fundamentally shapes phagocytic success and suggest that immune cells may exploit mechanical cues to recognize among different classes of soft targets.
  5. EMBO J. 2026 Feb 03.
    CaMKII nucleates an osmotic protein supercomplex to induce cellular bleb expansion.
    Yuki Fujii, Yuji Sakai, Kenji Matsuzawa, Junichi Ikenouchi.
      Blebs are membrane protrusions formed when localized regions of the plasma membrane detach from the actin cortex, enabling outward expansion driven by intracellular pressure. These structures play critical roles in cell migration and proliferation. While cortical actin contraction has been proposed as the primary driver of cytoplasmic fluid influx during bleb expansion, our prior observations revealed compartmentalization of Ca²⁺ ions and specific proteins (e.g., Mena) within expanding blebs. The functional significance of these components remained unresolved. In this study, we demonstrate that elevated Ca²⁺ levels during bleb expansion induce the assembly of a protein superstructure built around the CaMKII holoenzyme, incorporating Mena and other regulatory proteins. This complex exhibits intrinsic osmotic activity, facilitating water influx and directly contributing to bleb expansion. These findings elucidate a novel mechanism underlying bleb expansion and provide new insights into the dynamic regulation of physicochemical properties of the cytoplasm.
    Keywords:  CaMKII; Cell Migration; Cytoplasmic Mechanics; Membrane Blebbing; Osmotically Driven Deformation
    DOI:  https://doi.org/10.1038/s44318-026-00703-5
  6. Res Sq. 2026 Jan 19. pii: rs.3.rs-8554870. [Epub ahead of print]
    A role for PaxB in regulating blebbing: experimental insights and theoretical perspectives from Dictyostelium discoideum.
    Zully Santiago, Brian Wey, Sobana Handi Dinuka Sewwandi de Silva, Jessica Reznik, Lamina Siby, Emmanuel Asante-Asamani, Derrick Brazill.
      Eukaryotic cells migrate using pressure-driven blebs or actin polymerization driven pseudopods, with cells preferring to bleb in compressed environments where high protrusion forces are required for movement. In mammals, paxillin is a focal adhesion protein that acts as a scaffold, linking integrins to the actin cytoskeleton and recruiting signaling molecules that regulate adhesion, cytoskeletal remodeling, and migration. Dictyostelium possesses a paxillin ortholog, PaxB, which shares conserved domains with mammalian paxillin and participates in processes such as adhesion, cytokinesis, development,and chemotaxis. However, the role of PaxB in blebbing is not well understood. Our work combines experimental and theoretical methods to elucidate the role of PaxB in blebbing. We use an under-agarose assay to collect data on paxB \((^{-})\) and wild-type cells under low and high compression and observe blebbing characteristics such as area and frequency. Our results point to a role for PaxB in regulating the relative size of blebs in response to increased compression through modulating the quality of the newly reformed cortex. Using a mathematical model, we show that decreasing the assembly rate of the cortex during bleb formation leads to relatively larger blebs, thus supporting our experimental findings. Together, our experiments and theory suggest a new role of PaxB in bleb-based chemotaxis.
    DOI:  https://doi.org/10.21203/rs.3.rs-8554870/v1
  7. J Extracell Biol. 2026 Feb;5(2): e70106
    Tissue-Specific Extracellular Vesicles Enriched From Circulation: Exploring the Liquid Biopsy Perspective.
    Biancamaria Pierri, Erez Eitan, Kenneth W Witwer, Diane B Re, Andrea A Baccarelli, Haotian Wu.
      Extracellular vesicles (EVs) released from tissues can be found in human biofluids. EVs reflect the phenotypic state of their cell of origin, carrying informative molecular biomarkers within and between tissues, and represent a promising target for liquid biopsy. However, the heterogeneity of EVs in their surface composition, luminal content, biogenesis and cellular origin poses a challenge for selective enrichment and validation of origin-specific EVs from the complex pool of circulating EVs. Another obstacle for translating EVs into liquid biopsy applications is the wide variety of separation and characterization methods, many of which lack standardization and reproducibility. In this review, we summarize current knowledge on tissue-specific EVs, highlighting their potential as indicators of tissue health and disease, as well as the existing challenges and limitations. From the existing literature, we identify a compelling need for better validation and reproducibility studies to support the development of tissue-specific EV applications. Identifying reliable tissue-enriched biomarkers, in particular, will be required to enable further insights into the physiology and pathology of EV source tissues. We also propose some considerations to address future guidelines on the topic. Together, these approaches will help to establish EV liquid biopsy applications as a keystone of translational medicine.
    Keywords:  biomarkers; cell communication; extracellular vesicles; liquid biopsy
    DOI:  https://doi.org/10.1002/jex2.70106
  8. bioRxiv. 2026 Jan 20. pii: 2026.01.17.699063. [Epub ahead of print]
    Chemotherapy-induced transfer of apoptotic machinery in extracellular vesicles between somatic and germ cells of the testis: mechanistic insights into onco-fertility preservation in pre-pubertal boys.
    Michael P Rimmer, Pamela Holland, Daniel C Rabe, Shannon L Stott, Christopher D Gregory, Rod T Mitchell.
      Extracellular vesicles (EVs) are increasingly recognized as critical mediators of intercellular communication, not least during cellular stress or therapy. While EV signalling is well-studied in various tissues, its role in the prepubertal testicular environment is not well understood. Chemotherapy, commonly used in paediatric oncology, poses a significant risk to spermatogonial stem cells (SSCs) and may affect long-term fertility in cancer survivors. The role of EVs in chemotherapy-induced testicular damage in these patients is unknown and may be important for developing new fertility preservation methods. Immortalised murine Sertoli (TM4) and spermatogonial (GC1-spg) cell lines were used to investigate cisplatin-induced changes in EV biogenesis, release, and function in an in vitro model of the prepubertal testicular microenvironment. Our findings indicate that cisplatin significantly increases EV secretion and internalisation by recipient cells. Notably, EVs from cisplatin-exposed Sertoli cells exhibit a novel pro-apoptotic phenotype when co-cultured with chemotherapy-naïve Sertoli cells. Proteomic profiling of these EVs shows enrichment of apoptosis-regulatory proteins including caspases, activating Caspase-3/7 in recipient Sertoli cells. Conversely, germ cells exposed to Sertoli cell-derived EVs displayed reduced levels of apoptosis as well as a chemoprotective role to germ cells undergoing treatment with cisplatin. These findings indicate a dual role for Sertoli cell-derived EVs in mediating (1) apoptosis in Sertoli cells and (2) protection of germ cells following cisplatin exposure. The presence of pro-apoptotic molecules, especially caspases, in chemotherapy-induced Sertoli cell EVs provides mechanism for the induction of somatic cell apoptosis. Furthermore, their protective effects on germ cells demonstrate the complexity of EV-mediated signalling between testicular cell types. Manipulating EV biogenesis and cargo loading could be a promising approach to reduce chemotherapy-related gonadotoxicity and preserve fertility in childhood cancer patients.
    DOI:  https://doi.org/10.64898/2026.01.17.699063
  9. bioRxiv. 2026 Jan 21. pii: 2026.01.21.700789. [Epub ahead of print]
    Septins buffer actomyosin forces to protect the nucleus from genotoxic mechanical stress.
    Franklin Mayca-Pozo, Sarah M Butts, Andrew W Schaefer, Cristina Montagna, Elias T Spiliotis.
      Invasively migrating cells thread their nucleus through confined interstitial spaces. How cells protect the nucleus from intracellular forces is poorly understood. Here, we show that the septin cytoskeleton buffers the actomyosin forces that power nuclear movement. Septin filaments comprising SEPT9, a septin amplified in breast cancer, align with perinuclear actomyosin cables which exhibit higher tensile stress during 3D confined migration through narrower pores. SEPT9 depletion amplifies actin stress during confined migration and after myosin II hyper-activation in non-migrating cells causing actin and nuclear envelope ruptures. Following confined migration, DNA breaks, nuclear blebs, micronuclei and cell death increase in SEPT9-depleted cells, phenotypes rescued by the oncogenic SEPT9 isoform 1. Clinicogenomic data reveal that SEPT9 amplification associates with lower genomic alteration in aggressive breast tumors and higher patient mortality. We propose that septins are a mechanoprotective element of the cytoskeleton, and SEPT9 amplification enhances tumor cell survival by preventing nuclear damage.
    DOI:  https://doi.org/10.64898/2026.01.21.700789
This page is being maintained by Thomas Krichel. It was last updated on 2026‒02‒08 at 9:01.