bims-ceblev 2026-02-01 papers

bims-ceblev

Biomed News

on Cell mechanics, blebs, and extracellular vesicles

Issue of 2026–02–01
ten papers selected by
Juan Manuel García Arcos, École Polytechnique Fédérale de Lausanne

Characterization of Large Extracellular Vesicles Released by Apoptotic and Pyroptotic Cells.
Large extracellular vesicles regulate endothelial angiogenic potential via paracrine and autocrine signaling.
Integrating mass spectrometry-based multi-omic signatures of extracellular vesicles: from discovery to clinical translation.
Insights into lysosome-related organelle biogenesis: melanosome as a model organelle.
Circulating Fibrocytes: Cellular Mediators of Tissue Fibrosis.
Mechanisms and therapeutic potential of migrasomes in neurological disorders.
Chemical analysis of extracellular vesicles by synchrotron-based X-ray imaging and scattering techniques: a review and perspective.
Small equatorial deformation of homogeneous spherical fluid vesicles.
Lipid scrambling via TMEM16F mediates the formation and release of extracellular vesicles.
Deciphering the nanoscale architecture of presynaptic actin using a micropatterned presynapse-on-glass model.

Int J Mol Sci. 2026 Jan 19. pii: 976. [Epub ahead of print]27(2):

Characterization of Large Extracellular Vesicles Released by Apoptotic and Pyroptotic Cells.

Delaram Khamari, Nora Fekete, Ririka Tamura, Raeeka Khamari, Agnes Kittel, Bence Nagy, Luigi Menna, Zsuzsanna Darula, Alicia Galinsoga, Eva Hunyadi-Gulyas, Maximilien Bencze, Edit I Buzas.

  Extracellular vesicles (EVs) are emerging as key factors in maintaining cellular homeostasis, critical mediators of intercellular communication, potential biomarkers, and therapeutic tools. While small EVs have been extensively characterized, the molecular signatures of large EVs (including those generated during regulated cell death pathways) remain poorly defined. Here, we investigated the characteristics of large EVs released during apoptosis and pyroptosis by human monocytic cell lines (THP-1 and U937). Apoptosis was induced by staurosporine and blocked using the pan-caspase inhibitor Q-VD-OPh, whereas pyroptosis was triggered by LPS/nigericin and inhibited with a selective NLRP3 inhibitor. We found that both forms of regulated cell death markedly enhanced the release of large EVs. Both apoptotic and pyroptotic large EVs showed increased Annexin V binding and decreased CD9 expression compared with those released by healthy cells. Large EVs derived from apoptotic and pyroptotic cells exhibited distinct proteomic profiles. Pyroptotic large EVs carried interacting protein networks of RNA-binding proteins and chromatin-associated proteins many of which are known damage-associated molecular patterns or alarmins. In contrast, we found that a subpopulation of apoptotic large EVs was characterized by the presence of dsDNA, and active caspase-3/7. Together, our data shed light on the specific protein cargo of large EVs released by cells during apoptosis and pyroptosis. This study identifies candidate markers of large EVs released by dying cells and may enhance our understanding of the role of EVs in regulated cell death.

Keywords:  apoptosis; cell death; extracellular vesicles; pyroptosis

DOI:  https://doi.org/10.3390/ijms27020976
J Biol Chem. 2026 Jan 23. pii: S0021-9258(26)00063-3. [Epub ahead of print] 111193

Large extracellular vesicles regulate endothelial angiogenic potential via paracrine and autocrine signaling.

Grace Richmond, Rose Nguyen, Alanna Sedgwick, Jeffrey S Schorey, Crislyn D'Souza-Schorey.

  Angiogenesis, a process typically associated with tumor growth and development, is often linked to advanced disease and poor clinical outcomes. Tumor cells establish a pro-angiogenic microenvironment through the release of paracrine signaling mediators including extracellular vesicles (EVs). EVs have been shown to facilitate intercellular communication and encompass a diverse range of secreted vesicles, including small EVs (sEVs) which range in size from ∼60 to 100nm and large EVs (L-EVs) which are even more diverse and range from 200nm to >1μm in size. Despite advancements in anti-angiogenic cancer therapies, such as bevacizumab, late-stage tumors, including advanced melanomas, exhibit mixed clinical responses. In this study, we elucidate a unique role for melanoma-derived L-EVs in promoting bevacizumab-insensitive endothelial angiogenic phenotypes. This L-EV-mediated increase in endothelial tube formation is sensitive to the effects of sorafenib, a multi-kinase inhibitor, but not SU5416, a selective VEGF-receptor inhibitor. We also demonstrate that melanoma L-EVs contain VEGF as luminal cargo and induce paracrine effects by modulating the endothelial EV secretome. The release from endothelial cells of soluble VEGF, EVs, and pro-angiogenic cytokines such as IL-8, MIF, and PAI-1 drive sustained endothelial tube formation through autocrine signaling. Finally, we show that EV subtypes have distinct effects on the acquisition of angiogenic phenotypes and their roles vary with tumor type. These findings provide new insight into the mechanisms of angiogenic therapy resistance in melanoma and demonstrate the differential functions of EV subtypes in angiogenesis across tumor types.

Keywords:  cancer; endothelial cells; extracellular vesicles; melanoma; tumor microenvironment

DOI:  https://doi.org/10.1016/j.jbc.2026.111193
Clin Transl Immunology. 2026 ;15(1): e70078

Integrating mass spectrometry-based multi-omic signatures of extracellular vesicles: from discovery to clinical translation.

Akila Wijerathna-Yapa, Dimitri Aubert, Arutha Kulasinghe.

  Extracellular vesicles (EVs) are increasingly recognised as key mediators of intercellular communication and disease progression. Their capacity to carry bioactive molecules, namely proteins, lipids and metabolites, reflects the physiological and pathological states of their cells of origin, making them surrogates for diagnostic, prognostic and therapeutic endpoints. Recent advances in mass spectrometry have enabled comprehensive, high-resolution profiling of EVs across multiple omics layers. Proteomics has uncovered both conserved and disease-specific protein markers; lipidomics has revealed structurally distinct membrane compositions influencing EV stability and function; and metabolomics has captured dynamic snapshots of cellular metabolism. However, significant challenges persist for standardisation and interpretation of EVs, which include variation in EV isolation purity, scalability, EV heterogeneity and cross-study comparability. This perspective critically synthesises findings from recent EV multi-omics studies and proposes a conceptual framework for integrating these omics layers to better define EV identity and functionality. We highlight emerging clinical applications and outline future directions involving single-vesicle omics and the rational engineering of therapeutic EVs. The integration of multi-omics approaches with translational aims holds promise for advancing EVs from experimental tools to new pillars of precision medicine.

Keywords:  exosomes; extracellular vesicles; liquid biopsy; mass spectrometry; multi‐omics

DOI:  https://doi.org/10.1002/cti2.70078
Front Cell Dev Biol. 2025 ;13 1758081

Insights into lysosome-related organelle biogenesis: melanosome as a model organelle.

Duarte C Barral, Cédric Delevoye, Lionel Larue, Miguel C Seabra, Graça Raposo, Subba Rao Gangi Setty.

  Lysosome-related organelles (LROs) encompass specialized intracellular compartments that share features with lysosomes while fulfilling distinct physiological roles, with melanosomes representing the best-studied example. Melanosome biogenesis relies on coordinated trafficking, sorting, and membrane remodeling mechanisms that diverge from the canonical endolysosomal pathways. These organelles ultimately serve as the primary sites of melanin synthesis and deposition. In the skin, melanin is produced by melanocytes and transferred to keratinocytes, where it achieves its essential photoprotective role. Melanin is a remarkably diverse and ancient polymer, with eumelanin, pheomelanin, and neuromelanin constituting the major mammalian forms. Understanding melanin biology also requires tracing the origins of melanocytes, which were once thought to derive exclusively from the neural crest but are now known to arise from multiple embryonic lineages. This expanded view of melanocyte ontogeny has revealed unexpected pigment cell populations in several internal organs. Beyond these developmental aspects, melanin performs multifaceted physiological functions that extend far beyond photoprotection of the skin. Here, we discuss the current knowledge on the origin of melanosomes from endosomal precursors, the transfer of melanin from melanocytes to keratinocytes, and its fate in these recipient cells within the epidermis. Additionally, the intriguing mysteries surrounding melanosomes in the retinal pigment epithelium are addressed, as well as the broader diversity, origins, and physiological roles of melanin in other cell types. Taken together, these perspectives highlight the melanosome as both a model LRO and an organellar hub for deciphering melanin diversity, cellular origins, and the wide-ranging physiological roles of this pigment in vertebrate biology.

Keywords:  keratinocyte; lysosome-related organelle; melanin; melanocyte; melanosome biogenesis; retinal pigment epithelium; skin pigmentation and photoprotection

DOI:  https://doi.org/10.3389/fcell.2025.1758081
Int J Mol Sci. 2026 Jan 06. pii: 557. [Epub ahead of print]27(2):

Circulating Fibrocytes: Cellular Mediators of Tissue Fibrosis.

Xinya Guo, Jianyu Lu, Yiyao Du, Zhaofan Xia, Shizhao Ji.

  Fibrosis is a pathological condition resulting from an excessive tissue response during the repair process, often affecting various tissues such as the skin, organs, and joints, posing a significant threat to global health. Researchers have made substantial efforts to explore the endogenous mechanisms underlying fibrosis in recent years and have developed several therapeutic strategies to block this process. Historically, research on fibrotic diseases has focused on identifying highly relevant therapeutic targets and developing effective antifibrotic drugs. However, due to the complexity of the mechanisms of fibrosis and its effector cells, the effectiveness of antifibrotic therapies remains limited. With the advancement of high-throughput omics technologies and machine learning tools, we now have a clearer understanding of cellular heterogeneity, intercellular interactions, and the specific roles of cells in various biological processes. This enables tracking the trajectory of different cell types during the fibrotic process, facilitating early identification and discovery of new targets for fibrosis treatment, and conducting more precise targeted research. Supported by these novel technologies, numerous studies have revealed that, in addition to normal fibroblasts, a group of bone marrow-derived fibrocytes also contributes to the fibrosis of both parenchymal and non-parenchymal organs and tissues. Circulating fibrocytes are hematopoietic-derived cells that are recruited to injury sites during injury, disease, and aging, acting as participants in inflammation and tissue repair, and directly or indirectly promoting fibrosis in various tissues throughout the body. This review summarizes the general characteristics of circulating fibrocytes, the molecular mechanisms involved in their recruitment to different tissues, the process of their differentiation into fibroblasts, their potential roles in various diseases, and the latest research developments in this field. Given the key role of circulating fibrocytes in fibrosis across multiple tissues, they may serve as promising targets for the development of novel antifibrotic therapies.

Keywords:  circulating fibrocytes; fibrosis

DOI:  https://doi.org/10.3390/ijms27020557
Cell Signal. 2026 Jan 23. pii: S0898-6568(26)00039-2. [Epub ahead of print]141 112389

Mechanisms and therapeutic potential of migrasomes in neurological disorders.

Simeng Zhang, Yanhua Yang, Tiancheng Zhang, Ye Pan, Qinggang Xu, Peng Lü.

  Migrasomes, a recently identified class of organelles, form at the tips or intersections of retraction fibers during cell migration. These structures carry various bioactive cargoes, including proteins, mRNAs, and cytokines, and play significant roles in intercellular communication, immune regulation, and tissue homeostasis. As specialized membrane structures generated during cell migration, migrasomes are not only involved in physiological processes such as embryonic development and vascular homeostasis but are also critically implicated in the pathogenesis of neurological disorders. In this review, we outline the fundamental biological characteristics and functions of migrasomes, provide an in-depth analysis of their pathological mechanisms in neurological diseases, and evaluate their clinical potential as novel diagnostic biomarkers, drug delivery vehicles, and therapeutic targets. Overall, this review offers new perspectives for precision diagnostics and therapeutics of neurological diseases and lays a foundation for diagnosing and treating migrasome-related pathologies.

Keywords:  Migrasomes; Neurological disorders; Pathological mechanisms; Therapeutic targets

DOI:  https://doi.org/10.1016/j.cellsig.2026.112389
Front Bioeng Biotechnol. 2025 ;13 1769106

Chemical analysis of extracellular vesicles by synchrotron-based X-ray imaging and scattering techniques: a review and perspective.

Li Huang, Yan Chen, Xiutian Guo, Limin Zhou.

  Extracellular vesicles (EVs) are nanoscale lipid bilayer-enclosed particles released by cells, which have been explored as pivotal mediators for intercellular communication, biomarkers for diseases and nano-carriers for drug delivery. Unraveling their structural and chemical heterogeneity is crucial for understanding the biogenesis, cargo sorting, and functional mechanisms of EVs. However, by far it remains challenging to characterize the intrinsic physicochemical properties of EVs due to their varied intracellular origins, poly-disperse size distribution and dynamic membrane organization. Conventional imaging and light scattering methods either lack the chemical sensitivity or suffer from labeling artifacts. Here in this review, we summarize research work using synchrotron-based X-ray imaging and scattering techniques to resolve the chemical structural complexity of EVs with intrinsic chemical specificity and enhanced sensitivity. The feasibility and effectiveness of X-ray imaging and scattering tools on quantifying critical structural parameters of EVs including morphology, core-shell and bilayer structure is discussed. We hope it will inspire future in-depth work to bridge the gap between structural and biological functionality in EVs research.

Keywords:  X-ray photoelectron spectroscopy; chemical analysis; extracellular vesicles; small angle X-ray scattering; soft x-ray microscopy

DOI:  https://doi.org/10.3389/fbioe.2025.1769106
Eur Phys J E Soft Matter. 2026 Jan 28. 49(1-2): 7

Small equatorial deformation of homogeneous spherical fluid vesicles.

Andrés Solís-Cuevas, Pablo Vázquez-Montejo.

We examine the reaction of a homogeneous spherical fluid vesicle to the force exerted by a rigid circular ring located at its equator in the linear regime. We solve analytically the linearized first integral of the Euler-Lagrange equation subject to the global constraints of fixed area and volume, as well as to the local constraint imposed by the ring. We determine the first-order perturbations to the generating curve of the spherical membrane, which are characterized by the difference of the radii of the membrane and the ring, and by a parameter depending on the physical quantities of the membrane. We determine the total force that is required to begin the deformation of the membrane, which gives rise to a discontinuity in the curvature of the membrane across the ring.

DOI: https://doi.org/10.1140/epje/s10189-025-00553-9
Mol Biol Cell. 2026 Jan 28. mbcE25050245

Lipid scrambling via TMEM16F mediates the formation and release of extracellular vesicles.

Trieu Le, Maria Eugenia Perez Collado, Yu Meng Li, Amra Saric, Joost C M Holthuis, Sergio Grinstein, Spencer A Freeman.

The ubiquitous and highly conserved programmed cell death pathways that are essential for tissue development and homeostasis are accompanied by distinct morphological alterations. Apoptotic cells undergo fragmentation that is concomitant with the exposure of phosphatidylserine (PS) on the membrane surface. Large fragments, called apoptotic bodies, as well as much smaller and more numerous vesicles are released. While the molecular mechanisms underlying apoptotic body formation have been explored, much less is known about vesicle biogenesis. We used an inducible, active form of TMEM16F to determine the role of lipid scrambling in vesiculation, separately from other apoptotic signaling events. Plasmalemmal lipid scrambling sufficed to release apoptotic-like vesicles without causing changes in cytosolic calcium or the submembrane cytoskeleton. The scrambled bilayer showed pronounced segregation of exofacial lipids and redistribution of detectable cholesterol to the inner leaflet. The clustering of raft-associated components with bulky headgroups-typified by glycophosphatidylinositol-linked proteins-formed domains of outward (convex) curvature, while regions of accumulation of phosphatidylethanolamine (PE) generated inward (concave) curvature that facilitated the scission of vesicles. Thus, scrambling of plasma membrane lipids suffices to induce regions of acute membrane curvature and facilitates detachment of vesicles analogous to those released from the surface of apoptotic cells.

DOI: https://doi.org/10.1091/mbc.E25-05-0245
J Neurosci. 2026 Jan 29. pii: e1741242026. [Epub ahead of print]

Deciphering the nanoscale architecture of presynaptic actin using a micropatterned presynapse-on-glass model.

Sofia Tumminia, Louisa Mezache, Theresa Wiesner, Fanny Boroni-Rueda, Christopher Parperis, Benoit Vianay, Manuel Théry, Marie-Jeanne Papandréou, Christophe Leterrier.

Chemical synapses are fundamental units for the transmission of information throughout the nervous system. The cytoskeleton allows to build, maintain and transform both pre- and postsynaptic contacts, yet its organization and the role of its unique synaptic nanostructures are still poorly understood. Here we present a presynapse-on-glass model based on cultured neurons from rat pups of either sex. Presynaptic specializations are robustly induced along axons by micropatterned dots of neuroligin, allowing the controlled orientation and easy optical visualization of functional induced presynapses. We demonstrate the relevance and usefulness of this presynapse-on-glass model for the study of presynaptic actin architecture, showing that a majority of induced presynapses are enriched in actin, with this enrichment being correlated to higher synaptic cycling activity. We confirm our previous results on bead-induced presynapses by identifying distinct actin nanostructures within presynapses: corrals, rails and mesh. Furthermore, we leverage the controlled orientation of the presynapse-on-glass model, visualizing the arrangement of these actin structures relative to the active zone nanoclusters using multicolor 3D Single Molecule Localization Microscopy (SMLM), and relative to the sub-diffractive localization exocytic events using a correlative live-cell and SMLM approach.Significance statement The actin cytoskeleton plays important but poorly understood roles at presynapses, fundamental compartments for communication in the nervous system. We developed a presynapse-on-glass model to induce isolated, optically accessible presynaptic specializations along the axon of cultured neurons. This model recapitulates the presynaptic actin enrichment and distinct nanostructures we previously uncovered using presynapses induction by large beads. The controlled orientation of presynapses in our new model allows to go further: we visualized the nanoscale arrangement of actin and presynaptic components by multicolor nanoscopy, and could link actin nanostructures to the precise location of synaptic vesicle release thanks to a correlative live-cell/super-resolution microscopy approach. This demonstrates the relevance of our model for deciphering the nano-architecture of presynapses and understand their molecular functioning.

DOI: https://doi.org/10.1523/JNEUROSCI.1741-24.2026