Biology subjects

Wodrascka, F.

Publications and source records attributed to Wodrascka, F..

4 recordsLinked to original sources

bioRxiv2026

Local mechanical heterogeneity drives epidermal cell delamination

Delamination within stratified epithelia like the skin epidermis describes the detachment and upward motion of cells originating from the basal layer. Despite its fundamental importance for tissue development, homeostatic regeneration and repair, the mechanisms that drive delamination remain a longstanding open question. Upward motion follows cell shape changes, which are inherently driven by physical forces, but their role is elusive. Here, we investigate delamination in stratifying keratinocytes by combining imaging, force measurements and theoretical modeling. We identify a local change in force balance between differentiating cells and their environment as the key step initiating delamination. Within a homogeneous cell layer with apically polarized contractility, differentiation leads to actomyosin remodeling, redistributing cellular force exertion to the basal side. Such mechanical heterogeneity then results in differentiating cells experiencing and inward basal and outward apical forces that manifest in the formation of a +1 force defect and promote shape changes culminating in upward motion. Simultaneously, delaminating cells actively pull on their underlying neighbors, generating convergent tissue flows which close the basal layer below. Together, we propose a general physical description of delamination initiation, which may act across various multilayered epithelia.

biophysics↗

bioRxiv2026

A principal-stress rule for cell division in epithelia

Dense active materials, from cellular tissues to jammed and glassy systems, must continuously relieve internal mechanical stress to remain structurally stable as they are driven far from equilibrium. In epithelial tissues, this relief occurs through cell division, yet what sets the geometry of this structural remodeling event has, for over a century, been attributed to a purely geometric principle: Hertwigs rule, whereby cells divide along their long axis. We show that as epithelial tissues densify and cell shape anisotropy collapses, this geometric rule is superseded by a mechanical one in which dense epithelia relieve anisotropic stress by cells dividing along their principal axis, independent of the tissues isotropic stress state. Using direct force measurement and stress inference, we show that stress orientation, rather than cell shape, governs the axis of cell division across mechanically distinct systems, from fluid-like to jammed monolayers and structurally heterogeneous organoids, remaining predictive precisely where the classical geometric rule fails. This stress-oriented remodeling is reciprocally coupled to the materials mechanical state: anisotropic stress accelerates the underlying remodeling rate, while each remodeling event locally dissipates the stress that triggered it, closing a negative feedback loop. This "principal-stress rule" recasts epithelial cell division as a stress-relief mechanism intrinsic to dense active matter, providing a general mechanical framework linking internal stress, structural remodeling, and homeostasis in living materials.

biophysics↗

bioRxiv2026

Mechanical Tension Actively Triggers RhoA-Mediated Cell Extrusion

Cell extrusion is a fundamental process in tissue homeostasis, morphogenesis, and cancer progression, facilitating the removal of cells either alive or through apoptosis. While biochemical signaling pathways are known to regulate extrusion, recent advances have underscored the importance of mechanical forces in this process. Here, using optogenetic control of RhoA activation in epithelial monolayers combined with Bayesian Inversion Stress Microscopy (BISM) and three-dimensional cell-based modeling, we uncover a counterintuitive mechanism whereby elevated tension, instead of stabilizing the monolayer, actively drives extrusion in highly contractile cells. We show that local RhoA activation enhances myosin II-dependent contractility and F-actin reorganization, which promotes cell stiffening, resulting in localized tension buildup. The ensuing tensile stress amplifies vertical mechanical fluctuations, which in turn trigger cell extrusion. Remarkably, these tension-induced extrusions occur both apically and basally. Furthermore, our findings show that RhoA-mediated contractility is not merely an effector of extrusion but also an active promoter of basal extrusion, independently of caspase activation. Our study demonstrates that tensile stress can directly initiate extrusion events and bias their outcome toward apical or basal fates. By identifying tension as a driver rather than a suppressor of extrusion, this work revises current models of epithelial homeostasis and highlights mechanical control as a targetable axis in disease and regeneration.

cell biology↗

bioRxiv2025

Osmotic pressure induces unexpected relaxation of contractile 3D microtissue

Cell contraction and proliferation, matrix secretion and external mechanical forces induce compression during embryogenesis and tumor growth, which in turn regulate cell proliferation, metabolism or differentiation. How compression affects tissue contractility, a hallmark of tissue function, is however unknown. Here we apply osmotic compression to microtissues of either mouse colon adenocarcinoma CT26 cells, mouse NIH 3T3 fibroblasts, or human primary colon cancer-associated fibroblasts. Microtissues are anchored to flexible pillars that serve as force transducers. We observe that low-amplitude osmotic compression induces a rapid relaxation of tissue contractility, primed by the deformation of the extracellular matrix. Furthermore, we show that this compression-induced relaxation is independent of the cell type, proportional to the initial tissue contractility, and depends on RhoA-mediated myosin activity. Together, our results demonstrate that compressive stress can relax active tissue force, and points to a potential role of this feedback mechanism during morphogenetic events such as onco- or embryogenesis.

biophysics↗