Biology subjects

Ouzeri, A.

Publications and source records attributed to Ouzeri, A..

4 recordsLinked to original sources

bioRxiv2025

Multiscale wrinkling dynamics in epithelial shells

Thin shells buckle and wrinkle when compressed. While this behavior is generally detrimental in engineering, it has been widely implicated in epithelial morphogenesis and patterning during development. Yet the rules governing buckling of active viscoelastic shells like epithelia remain unclear. Here we delineate those rules by combining an experimental system that allows us to sculpt epithelial shells and subject them to controlled deflation with a 3D computational model linking cytoskeletal dynamics to tissue mechanics. Experiments and simulations across several orders of magnitude in time and space reveal that buckling emerges for fast deflation relative to the cortexs relaxation time, and is suppressed by high contractility. We show, further, that the tissue develops wrinkle patterns with different degrees of symmetry breaking that depend on its size and viscous confinement. Strikingly, we find that epithelial buckling is a multiscale phenomenon involving long-lived supracellular folds but also short-lived subcellular wrinkles in the actin cortex. Finally, by forming epithelial shells with anisotropic curvature we rationally direct buckling into predictable wrinkle patterns. Our study shows that epithelial tissues can be understood as hierarchical materials with mechanical instabilities that can be harnessed to engineer epithelial morphogenesis.

biophysics↗

bioRxiv2025

Theory of multiscale epithelial mechanics under stretch: from active gels to vertex models

Epithelial monolayers perform a variety of mechanical functions, which include maintaining a cohesive barrier or developing 3D shapes, while undergoing stretches over a wide range of magnitudes and loading rates. To perform these functions, they rely on a hierarchical organization, which spans molecules, cytoskeletal networks, adhesion complexes and junctional networks up to the tissue scale. While the molecular understanding and ability to manipulate cytoskeletal components within cells is rapidly increasing, how these components integrate to control tissue mechanics is far less understood, partly due to the disconnect between theoretical models of sub-cellular dynamics and those at a tissue scale. To fill this gap, here we propose a formalism bridging active-gel models of the actomyosin cortex and 3D vertex-like models at a tissue scale. We show that this unified framework recapitulates a number of seemingly disconnected epithelial time-dependent phenomenologies, including stress relaxation following stretch/unstretch maneuvers, active flattening after buckling, or nonreciprocal and non-affine pulsatile contractions. We further analyze tissue dynamics probed by a novel experimental setup operating in a pressure-controlled ensemble. Overall, the proposed framework systematically connects sub-cellular cortical dynamics and tissue mechanics, and ties a variety of epithelial phenomenologies to a common sub-cellular origin.

biophysics↗

bioRxiv2025

Continuum theory for the mechanics of curved epithelial shells by coarse-graining an ensemble of active gel cellular surfaces

Epithelial tissues undergo complex morphogenetic transformations driven by cellular and cytoskeletal dynamics. To understand the emergent tissue mechanics resulting from sub-cellular mechanisms, we formulate a fully nonlinear continuum theory for epithelial shells that coarse-grains an underlying 3D vertex model, whose surfaces are in turn patches of active viscoelastic gel undergoing turnover. Our theory relies on two ingredients. First, we relate the deformation of apical, basal and lateral surfaces of cells to the continuum deformation of the tissue mid-surface and a thickness director field. We explore two variants of the theory, a Cosserat theory accommodating through-thickness tilt of cells, and a Kirchhoff theory assuming that lateral cell surfaces remain perpendicular to the mid-surface. Second, by adopting a variational formalism of irreversible thermodynamics, we construct an effective Rayleighian functional of the tissue constrained by the cellular-continuum kinematic relations, which therefore depends on continuum fields only. This functional allows us to obtain the governing equations of the continuum theory and is the basis for efficient finite element simulations. Verification against explicit 3D cellular model simulations demonstrates the accuracy of the proposed theory in capturing epithelial buckling dynamics. Furthermore, we show that the Cosserat theory is required to model tissues exhibiting apicobasal asymmetry of active tension. Our work provides a general frame-work for further studies integrating refined subcellular models into continuum descriptions of epithelial mechanobiology.

biophysics↗

bioRxiv2022

Mapping mechanical stress in curved epithelia of designed size and shape

The function of organs such as lungs, kidneys and mammary glands relies on the three-dimensional geometry of their epithelium. To adopt shapes such as spheres, tubes and ellipsoids, epithelia generate mechanical stresses that are generally unknown. Here we engineered curved epithelial monolayers of controlled size and shape and mapped their state of stress. We designed pressurized epithelia with circular, rectangular and ellipsoidal footprints. We developed a computational method to map the stress tensor in these epithelia. This method establishes a direct correspondence between epithelial shape and mechanical stress without assumptions of material properties. In epithelia with spherical geometry spanning more than one order of magnitude in radius, we show that stress weakly increases with areal strain in a size-independent manner. In epithelia with rectangular and ellipsoidal cross-section we found pronounced stress anisotropies consistent with the asymmetric distribution of tractions measured at the cell-substrate contact line. In these anisotropic profiles, cell shape tended to align with the direction of maximum principal stress but this alignment was non-universal and depended on epithelial geometry. Besides interrogating the fundamental mechanics of epithelia over a broad range of sizes and shapes, our approach will enable a systematic study of how geometry and stress influence epithelial fate and function in three-dimensions.

biophysics↗