Biology subjects

Kanchanawong, P.

Publications and source records attributed to Kanchanawong, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Senescence-induced Spatio-temporal Re-organization of the Nuclear Lamina Dynamic Landscape at Single-molecule Level in Live Human RPE Cells

A defining hallmark of cellular senescence is the extensive remodeling of the nuclear lamina (NL) in both structure, composition, and its interactions with lamina-associated genomic domains. However, how such senescence-induced changes could quantitatively impact the spatio-temporal dynamics of NL interactions at the single-molecule level remain poorly understood. Herein, using human retinal pigment epithelium (RPE) cells as model system, we establish a robust, chemically inducible cellular senescence model capable of recapitulating key signatures of the senescence-associated phenotype. Senescent RPE cells exhibit distinct alteration patterns in the expression of various NL components, including lamin B receptor (LBR) and emerin, two key mediators of NL-chromatin interactions. Importantly, live-cell diffusion measurements via imaging FCS reveal globally enhanced mobility for both LBR and emerin, indicative of weakened NL anchoring in senescent cells. Single-molecule tracking and super-resolved STAR mapping further unveil distinct, multi-modal re-organization of their NL-binding dynamics in both space and time (especially in the form of LBR binding "hotspots" where multiple stable binding events cluster to effect more extended and prolonged interaction), in line with their respective expression-level alterations and differential lamin interactions. Moreover, correlative mapping uncovers a strong spatial coupling between reduced LBR mobility and highly condensed constitutive heterochromatin domains at the NL, which become dispersed during senescence. Collectively, these findings demonstrate the re-organization of NL dynamic landscape at single-molecule level as a critical and previously under-explored facet of senescence-induced NL remodeling, and point to a synergistic interplay between physical de-anchoring, dynamic attenuation of stable NL-binding and spatial restructuring of chromatin architecture in modulating NL-heterochromatin contacts to potentially effect global changes in senescence-associated gene expression.

biophysics↗

bioRxiv2026

Elimination of senescent cells by mechanical cell competition

Cellular senescence, a hallmark of aging, leads to the accumulation of apoptosis-resistant cells that compromise tissue homeostasis. While senescent cells are known to influence neighboring cells through the senescence-associated secretory phenotype (SASP), the precise nature of the interactions between senescent and normal cells remains elusive. Here we show that progerin-induced senescent cells undergo apoptosis when co-cultured with normal cells. This elimination requires direct cell-cell contact and is mediated by the JNK and p38-MAPK pathways, leading to p53 upregulation and p21 downregulation in progerin-expressing cells. Furthermore, neighboring normal cells exert persistent mechanical compression on progerin-expressing cells prior to their elimination, consistent with mechanical cell competition. In contrast, p16-induced senescent cells resist elimination under the same co-culture conditions, maintaining high p21 levels. Our findings reveal a non-cell-autonomous mechanism for senescent cell clearance, providing new insights into the maintenance of tissue homeostasis during aging.

cell biology↗

bioRxiv2025

Fibrillar adhesions are the primary integrin complexes shaped by matrix topography

Mechanisms of matrix topography recognition are poorly understood. Here, we show that 5{beta}1-integrin mediated fibrillar adhesions serve this function. While on planar substrates, their formation requires fibronectin secretion, tensins, and actomyosin contractility, these requirements are bypassed on nanotopographical features. While focal adhesions avoid these features, fibrillar adhesions rapidly align along pre-existing fibrous cell-derived matrix or electrospun nanofibers where they can then template fibronectin fibrils. Topography-induced fibrillar adhesions depend primarily on 5{beta}1-integrin clustering and disassemble upon cortical stiffening driven by myosin-II overactivation or increased membrane tension. We propose a generic theoretical model where the adhesion receptor favours the membrane and substrate planes to be tilted relative to each other. This model matches experimental observations of preferential 5{beta}1-integrin clustering along nanofibers and concave edges of large negative curvature along micro-ridges. These findings establish fibrillar adhesions as primary adhesion complexes that form independently of focal adhesions in response to matrix topography.

cell biology↗

bioRxiv2025

β-catenin controls Afadin cortical recruitment to regulate planar epithelial cell division

Mitotic spindle orientation is tightly controlled in epithelia to preserve polarized tissue architecture. Here, we uncover a previously unrecognized role of the adherens junction protein {beta}-catenin in regulating planar mitotic spindle positioning required for symmetric epithelial cell division. Using CRISPR/Cas9-mediated genome editing in MDCK cells, we found that {beta}-catenin--but not its close homolog {gamma}-catenin (plakoglobin)--is required for proper spindle orientation. Loss of {beta}-catenin disrupts astral microtubule anchorage and impairs the localization of LGN-NuMA spindle orientation machinery. Mechanistically, {beta}-catenin mediates spindle regulation via its N-terminal domain, independently of {beta}-catenin binding. We showed that the cortical recruitment of Afadin during mitosis depends on {beta}-catenin, but surprisingly, overexpression of either Afadin or ZO-1 rescue the spindle orientation in {beta}-catenin deficient cells by restoring cortical LGN. Afadin depletion or dominant-negative Afadin abolished ZO-1-mediated compensation, thereby establishing Afadin as the central cortical integrator, potentiated by {beta}-catenin, and operating through mass-action to recruit cortical LGN. Together, our findings define {beta}-catenin as an upstream regulator of the Afadin-based cortical-spindle linkage that coordinate the crosstalk between adherens junctions and mitotic geometry to ensure epithelial homeostasis.

cell biology↗

bioRxiv2025

Chip-Based 3D Interferometric Nanoscopy

Ultra-high resolution 3D single-molecule localization microscopy (SMLM) traditionally requires complex dual-objective lenses (4Pi) configurations to enhance axial (z) precision through interferometry. Here we present a streamlined chip-based alternative, Silicon-assisted interferometric Localization Microscopy (SiLM), which achieves comparable performance using a single-objective lens design. By combining tunable axial structured illumination field, arising from surface-generated excitation interference, with asynchronous interferometry, SiLM enhances axial localization precision to approximately twice that of the lateral (xy), comparable to 4Pi-based methods. Additionally, SiLM provides intrinsic axial self-referencing, offering dramatically improved robustness against mechanical drift. Our method is readily implementable on standard SMLM-capable microscopes and supports a broad range of applications including dual-color imaging, extended-depth imaging, and live-cell 3D single-molecule tracking. Using SiLM, we demonstrate accurate mapping of the stratified nanoscale architecture of integrin-based focal adhesions, establishing it as a powerful and accessible method for high-precision 3D structural cell biology.

biophysics↗

bioRxiv2025

Optogenetic control of mechanotransduction based on light-induced homodimerization of talin

Integrin-based cell adhesions (IACs) serve as primary sites where piconewton-scale actomyosin-generated mechanical forces are transmitted to the extracellular matrix (ECM), generating traction forces that drive cell-ECM responses including adhesion, migration, and mechano-signaling. Talin, a large (270 kDa) cytosolic adaptor protein, is the principal force-transmission protein in integrin-based adhesions, containing multiple mechanosensitive domains and protein-protein interaction sites that orchestrate molecular events in mechanosensing. As a highly modular multi-domain protein, talin has been identified as an effective target for chemogenetic and optogenetic manipulation of integrin-based mechanotransduction. However, a key limitation of previous approaches is the reliance on heterodimerization modules to control talin function, requiring the expression of two modified talin fragments. In practice, achieving precise expression levels in such a 2-component approach can be challenging, particularly when combined with other genetic tools. Since talin naturally contains a C-terminal dimerization domain that forms part of its actin-binding site, we reasoned that the molecularly engineered talin with a C-terminal optically-controlled homodimerizer could enable single-component optogenetic control of mechanotransduction. This approach would facilitate multiplexing with other molecular perturbations or experimental techniques. Here, we describe an opto-homodimerizable talin based on the pdDronpa1.2 optogenetic module, which enables optogenetic control of talin by a single construct. We demonstrate that light-induced talin dimerization promotes talin recruitment to IACs, adhesion formation, actin retrograde flow engagement, and downstream mechanotransduction signaling. Conversely, light-induced talin monomerization rapidly disassembles focal adhesions, disrupts talin-actin linkages, and accelerates actin retrograde flow, underscoring the critical roles of talin dimerization. Furthermore, our single-construct design allows facile multiplexing of optogenetic modulation of integrin-mediated mechanotransduction with super-resolution single-molecule tracking, revealing the essential role of talin dimerization for integrin v{beta}5 engagement.

cell biology↗

bioRxiv2024

AI-assisted imaging screening reveals mechano-molecular tissue organizers and network of signaling hubs.

Cadherin-mediated adhesions are crucial mechanical and signaling hubs that connect cells within a tissue and probe the mechanics of the surrounding environment. They constitute a physical link between the actin cytoskeleton of neighboring cells, providing the mechanical coordination needed for morphogenetic processes, tissue homeostasis, collective migration, and regeneration. Disruptions in adhesion mechanisms are closely linked to the breakdown of epithelial structure and the emergence of disease-related traits characteristic of cancer progression. The cadhesome network comprises over 170 structural and regulatory proteins involved in cadherin-mediated adhesion. While this network is essential for coordinating tissue responses to mechanical stress, its complexity has historically limited our understanding of how individual components contribute to force transmission and tissue homeostasis. Recent technological advances offer tools to investigate large molecular networks in cellular function and pathology (functional omics). Leveraging these advances, we developed an experimental and analytical platform combining high-throughput gene silencing, imaging, and artificial intelligence (AI) to systematically profile each role of each protein in tissue formation, mechanical stability, and response to induced tension. Using EpH4 cells as an epithelial tissue model, we performed systematic silencing in triplicate, capturing a range of tissue phenotypes under baseline and tension-inducing conditions. Machine learning methods were used to analyze complex imaging data, quantify tissue ruptures, characterize junctional organization, and measure tension states of the tissue. By incorporating machine learning algorithms, we automated image feature extraction, clustering, and classification, enabling an unprecedented quantitative evaluation of tissue mechanics at scale. Our machine learning models allowed us to identify significant patterns, including protein-specific responses to tension and their roles in tissue-level mechanical integrity. Finally, we constructed a protein interaction network detailing the roles of each protein, their physical interactions, and known links to cancer. The network analysis revealed three prominent mechanotransductive and signaling subnetworks centered around E-cadherin, EGFR, and RAC1. Our study provides a foundational framework for investigating mechanosensing proteins and it offers a scalable blueprint for discovering potential therapeutic targets in diseases like cancer, where tissue mechanics play a crucial role. TeaserAI-aided screening identifies key regulators of epithelial tissue mechanics, uncovering potential therapeutic targets in cancer.

cell biology↗

bioRxiv2024

Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling

The transitioning of neural stem cells (NSCs) between quiescent and proliferative states is fundamental for brain development and homeostasis. Defects in NSC reactivation are associated with neurodevelopmental disorders. Drosophila quiescent NSCs extend an actin-rich primary protrusion toward the neuropil. However, the function of the actin cytoskeleton during NSC reactivation is unknown. Here, we reveal the fine F-actin structures in the protrusions of quiescent NSCs by expansion and super-resolution microscopy. We show that F-actin polymerization promotes the nuclear translocation of Mrtf, a microcephaly-associated transcription factor, for NSC reactivation and brain development. F-actin polymerization is regulated by a signaling cascade composed of G-protein-coupled receptor (GPCR) Smog, G-protein q subunit, Rho1 GTPase, and Diaphanous (Dia)/Formin during NSC reactivation. Further, astrocytes secrete a Smog ligand Fog to regulate Gq-Rho1-Dia-mediated NSC reactivation. Together, we establish that the Smog-Gq-Rho1 signaling axis derived from astrocytes, a NSC niche, regulates Dia-mediated F-actin dynamics in NSC reactivation.

developmental biology↗

bioRxiv2024

Nano-clusters of ligand-activated integrins organize immobile, signalling active, nano-clusters of phosphorylated FAK required for mechanosignalling in focal adhesions

Transmembrane signalling receptors, such as integrins, organise as nanoclusters that are thought to provide several advantages including, increasing avidity, sensitivity (increasing the signal-to-noise ratio) and robustness (signalling above a threshold rather than activation by a single receptor) of the signal compared to signalling by single receptors. Compared to large micron-sized clusters, nanoclusters offer the advantage of rapid turnover for the disassembly of the signal. However, if nanoclusters function as signalling hubs remains poorly understood. Here, we employ fluorescence nanoscopy combined with photoactivation and photobleaching at sub-diffraction limited resolution of [~]100nm length scale within a focal adhesion to examine the dynamics of diverse focal adhesion proteins. We show that (i) subregions of focal adhesions are enriched in immobile population of integrin {beta}3 organised as nanoclusters, which (ii) in turn serve to organise nanoclusters of associated key adhesome proteins-vinculin, focal adhesion kinase (FAK) and paxillin, demonstrating that signalling proceeds by formation of nanoclusters rather than through individual proteins. (iii) Distinct focal adhesion protein nanoclusters exhibit distinct dynamics dependent on function. (iv) long-lived nanoclusters function as signalling hubs-wherein phosphorylated FAK and paxillin formed stable nanoclusters in close proximity to immobile integrin nanoclusters which are disassembled in response to inactivation signal by phosphatase PTPN12 (v) signalling takes place in response to an external signal such as force or geometric arrangement of the nanoclusters and when the signal is removed, these nanoclusters disassemble. Taken together, these results demonstrate that signalling downstream of transmembrane receptors is organised as hubs of signalling proteins (FAK, paxillin, vinculin) seeded by nanoclusters of the transmembrane receptor (integrin).

cell biology↗

bioRxiv2023

Intrinsic self-organization of integrin nanoclusters within focal adhesions is required for cellular mechanotransduction

Upon interaction with the extracellular matrix, the integrin receptors form nanoclusters as a first biochemical response to ligand binding. Here, we uncover a critical biodesign principle where these nanoclusters are spatially self-organized, facilitating effective mechanotransduction. Mouse Embryonic Fibroblasts (MEFs) with integrin {beta}3 nanoclusters organized themselves with an intercluster distance of [~]550 nm on uniformly coated fibronectin substrates, leading to larger focal adhesions. We determined that this spatial organization was driven by cell-intrinsic factors since there was no pre-existing pattern on the substrates. Altering this spatial organization using cyclo-RGD functionalized Titanium nanodiscs (of 100 nm, corroborating to the integrin nanocluster size) spaced at intervals of 300 nm (almost half), 600 nm (normal) or 1000 nm (almost double) resulted in abrogation in mechanotransduction, indicating that a new parameter i.e., an optimal intercluster distance is necessary for downstream function. Overexpression of -actinin, which induces a kink in the integrin tail, disrupted the establishment of the optimal intercluster distance, while simultaneous co-overexpression of talin head with -actinin rescued it, indicating a concentration-dependent competition, and that cytoplasmic activation of integrin by talin head is required for the optimal intercluster organization. Additionally, talin head-mediated recruitment of FHOD1 that facilitates local actin polymerization at nanoclusters, and actomyosin contractility were also crucial for establishing the optimal intercluster distance and a robust mechanotransduction response. These findings demonstrate that cell-intrinsic machinery plays a vital role in organizing integrin receptor nanoclusters within focal adhesions, encoding essential information for downstream mechanotransduction signalling.

cell biology↗

bioRxiv2023

Coordination of focal adhesion nanostructure and mechano-signaling drives cardiomyocyte differentiation

Focal adhesion (FA) organization and signaling are essential for cell growth and differentiation. However, the molecular mechanism that coordinates the FA signaling with cardiomyocyte differentiation has not been fully understood. Here, we provide empirical evidence that BNIP-2, a BCH-domain-containing protein, is the organizer of FA nanostructure that potentiates FA signaling and cell traction force transmission. Mechanistically, BNIP-2 serves as a scaffold for focal adhesion kinase (FAK), paxillin and vinculin to control their molecular organization and assembly/disassembly within FAs. Constitutively active phosphomimetic mutant FAK Y397D shows enhanced binding to BNIP-2, whereas the depletion of BNIP-2 reduces FAK phosphorylation and interaction between FAK and paxillin. Using H9c2 myoblasts and human embryonic stem cells as model systems, we show that BNIP-2 depletion results in aberrant FA dynamics with impairment of traction force, and changes in signature target genes, hereby impeding cardiomyocyte differentiation. BNIP-2 regulation of FA organization and dynamic is therefore pivotal to the mechanotransduction in cardiomyocyte differentiation, shedding new light to how FA-transduced force modulates cell growth and differentiation.

cell biology↗

bioRxiv2023

Ground-state pluripotent stem cells are characterized by Rac1-dependent Cadherin-enriched F-actin protrusions

Pluripotent Stem Cells (PSCs) exhibit extraordinary differentiation potentials that can be propagated in vitro and thus are commonly utilized in regenerative medicine. While different types of PSCs exist which correspond to different stages of pluripotency during embryogenesis, important aspects of their biology in terms of their cellular architecture and mechanobiology have been less well understood, thereby limiting their tissue engineering application potentials. Since the actin cytoskeleton is a primary determinant of cell mechanical properties, here we sought to investigate how the actin cytoskeleton may be differentially regulated in different states of pluripotency. Comparing ground-state naive mESCs and the corresponding converted prime epiblast stem cells (EpiSCs), we observed the actin cytoskeleton is drastically reorganized during the naive to prime pluripotency transition. Strikingly, we reported a distinctive actin organization that appears to be unique to the ground state mESCs, whereby the isotropic cortical networks are decorated with prominent actin-enriched structures which contain cadherin-based cell-cell junctional components, despite not locating at cell-cell junctions. We termed these structures "cadheropodia" and showed they arise from the cis-association of E-cadherin extracellular domain. Our measurements revealed that cadheropodia is under low mechanical tension and exhibits minimal calcium dependence, consistent with its putative dependence on cis-interaction. Further, we identified Rac1 as a negative regulator of cadheropodia whereby active Rac1 induces its fragmentation and dissociation of {beta}-catenin. Taken together, we described a novel actin-based structures in the ground-state mESCs, which may have potential roles in ground-state pluripotency and serve as useful structural markers to distinguish heterogeneous population of pluripotent stem cells.

cell biology↗

bioRxiv2023

Focal adhesions are controlled by microtubules through local contractility regulation

Microtubules regulate cell polarity and migration by local activation of focal adhesion turnover, but the mechanism of this process is insufficiently understood. Molecular complexes containing KANK family proteins connect microtubules with the major component of focal adhesions, talin. Local optogenetic activation of KANK1-mediated links which promoted microtubule targeting to individual focal adhesion resulting in its centripetal sliding and rapid disassembly. The sliding is preceded by a local increase of traction force due to accumulation of myosin-II and actin in the proximity of the focal adhesion. Knockdown of Rho activator GEF-H1 prevented development of traction force and abolished sliding and disassembly of focal adhesion upon KANK activation. Other players participating in microtubule-driven KANK-dependent focal adhesion disassembly include kinases ROCK and PAK, as well as microtubules/focal adhesions associated proteins Kinesin-1, APC and TAT. Finally, we propose a physical model of a microtubule-driven focal adhesion disruption involving local GEF-H1/RhoA/ROCK dependent activation of contractility which is consistent with experimental data.

cell biology↗

bioRxiv2021

ShareLoc - an open platform for sharing localization microscopy data

Novel insights and more powerful analytical tools can emerge from the reanalysis of existing data sets, especially via machine learning methods. Despite the widespread use of single molecule localization microscopy (SMLM) for super-resolution bioimaging, the underlying data are often not publicly accessible. We developed ShareLoc (https://shareloc.xyz), an open platform designed to enable sharing, easy visualization and reanalysis of SMLM data. We discuss its features and show how data sharing can improve the performance and robustness of SMLM image reconstruction by deep learning.

bioinformatics↗

bioRxiv2021

Actin polymerization and crosslinking drive left-right asymmetry in single cell and cell collectives

Deviations from mirror symmetry in the development of bilateral organisms are highly stereotypic and genetically predetermined, but their mechanisms are not sufficiently understood. At the cellular level, self-organization of the actin cytoskeleton results in chiral actin swirling, and cells in groups confined to micropatterns demonstrate chiral cell alignment. The relationship between individual and collective cell chirality is unclear, and molecular players involved remain essentially unidentified. Here, by screening major actin-associated proteins and deep-learning-based morphometric analysis of actin patterns, we found that knockdowns of specific actin polymerization regulators, such as mDia1, ARPC2, and cofilins 1&2, abolished chiral actin swirling, while depletion of profilin 1 and CapZ{beta}, reversed its direction in an actin crosslinker -actinin1-dependent manner. Analysis of these and other knockdowns and pharmacological treatments revealed a robust correlation between their effects on the chirality of individual cells and confined cell groups. Thus, actin-driven cell chirality may underlie tissue and organ asymmetry. One Sentence SummaryCell chirality determined by specific regulators of actin polymerization drives left-right asymmetry emergence in cell groups

cell biology↗

bioRxiv2019

Enhancement of endothelialization by topographical features is mediated by PTP1B-dependent endothelial adherens junctions remodeling

RationaleFailure of small synthetic vascular grafts is largely due to late endothelialization and has been an ongoing challenge in the treatment of cardiovascular diseases.\n\nObjectivePrevious strategies developed to promote graft endothelialization include surface topographical modulation and biochemical modifications. However, these have been met with limited success. Importantly, although the integrity of Endothelial Cell (EC) monolayer is crucial for endothelialization, the crosstalk between surface topography and cell-cell connectivity is still not well understood. Here we explored a combined strategy that utilizes both topographical features and pharmacological perturbations.\n\nMethods and resultWe characterized EC behaviors in response to micron-scale grating topography in conjunction with pharmacological perturbations of endothelial adherens junctions (EAJ) regulators. We studied the EA.hy 926 cell-cell junctions and monolayer integrity using the junctional markers upon the inhibitory effect of EAJ regulator on both planar and grating topographies substrates.\n\nWe identified a protein tyrosine phosphatase, PTP1B, as a potent regulator of EAJ stability. Next, we studied the physiologically relevant behaviors of EC using primary human coronary arterial endothelial cells (HCAEC). Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration to promote endothelialization.\n\nOur results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration and proliferation.\n\nConclusionThe synergistic effect of PTP1B inhibition and grating topographies could be useful for the promotion of endothelialization by enhancing EC migration and proliferation.

cell biology↗

bioRxiv2019

Mechanical Roles of Vinculin/β-catenin interaction in Adherens Junction

Mechanical force transmission through the adherens junctions (AJs) are highly regulated processes essential for multicellular organization of tissues. AJ proteins such as E-cadherin, -catenin, and vinculin have been shown to be sensing or bearing mechanical forces being transmitted between the actin cytoskeleton and the intercellular contacts. However, the molecular organization and connectivity of these components remains not well understood. Using a super-resolution microscopy approach, we report that vinculin, once activated, could form a direct structural connection with {beta}-catenin, which can bypass -catenin, one of the main mechanotransducers in AJs. Direct vinculin/{beta}-catenin interaction is capable of supporting mechanical tension and contributes to the stabilization of the cadherin-catenin complexes. These findings suggest a multi-step model for the force-dependent reinforcement of AJs whereby -catenin may serve as the initial catalytic activator of vinculin, followed by vinculin translocation to form a direct link between E-cadherin-bound {beta}-catenin and the actin cytoskeleton.

cell biology↗

bioRxiv2018

Molecular organization of integrin-based adhesion complexes in mouse Embryonic Stem Cells

The mechanical microenvironment serves as an important factor influencing stem cell differentiation. Mechanobiological responses depend strongly on actomyosin contractility and integrin-based cell-extracellular matrix (ECM) interactions mediated by adhesive structures such as focal adhesions (FAs). While the roles of FAs in mechanobiology have been intensively studied in many mesenchymal and migratory cell types, recently it has been recognized that certain pluripotent stem cells (PSCs) exhibited significantly attenuated FA-mediated mechanobiological responses. FAs in such PSCs are sparsely distributed and much less prominent in comparison to \"classical\" FAs of typical adherent cells. Despite these differences, insights into how FAs in PSCs are structurally organized to perform their functions are still elusive. Using mouse embryonic stem cells (mESCs) to study PSC-ECM interactions, here we surveyed the molecular composition and nanostructural organization of FAs. We found that despite being small in size, mESC FAs appeared to be compositionally mature, containing markers such as vinculin, zyxin, and -actinin, and dependent on myosin II contractility. Using super-resolution microscopy, we revealed that mESC FAs were organized into a conserved multilayer nanoscale architecture. However, the nanodomain organization was compressed in mESCs, with the force transduction layer spanning [~] 10 nm, significantly more compact than in FAs of other cell types. Furthermore, we found that the position and orientation of vinculin, a key mechanotransduction protein, were modulated in an ECM-dependent manner. Our analysis also revealed that while most core FA genes were expressed, the expression of LIM domain proteins was comparatively lower in PSCs. Altogether our results suggest that while core structural and mechanosensitive elements are operational in mESC FAs, their structural organization and regulatory aspects may diverge significantly from \"classical\" FAs, which may account for the attenuated mechanobiological responses of these cell types.

cell biology↗