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Biology subjects

Giomi, L.

Publications and source records attributed to Giomi, L..

4 recordsLinked to original sources

Hexanematic crossover in epithelial monolayers depends on cell adhesion and cell density

Changes in tissue geometry during developmental processes are associated with collective migration of cells. Recent experimental and numerical results suggest that these changes could leverage on the coexistence of nematic and hexatic orientational order at different length scales. How this multiscale organization is affected by the material properties of the cells and their substrate is presently unknown. In this study, we address these questions in monolayers of Madin-Darby canine kidney cells having various cell densities and molecular repertoires. At small length scales, confluent monolayers are characterized by a prominent hexatic order, independent of the presence of E-cadherin, monolayer density, and underlying substrate stiffness. However, all three properties affect the meso-scale tissue organization. The length scale at which hexatic order transits to nematic order, the "hexanematic" crossover scale, strongly depends on cell-cell adhesions and correlates with monolayer density. Our study demonstrates how epithelial organization is affected by mechanical properties, and provides a robust description of tissue organization during developmental processes.

biophysics↗

Stress fibers orient traction forces on micropatterns: A hybrid cellular Potts model study

Adhering cells exert traction forces on the underlying substrate. We numerically investigate the intimate relation between traction forces, the structure of the actin cytoskeleton, and the shape of cells adhering to adhesive micropatterned substrates. By combining the Cellular Potts Model with a model of cytoskeletal contractility, we reproduce prominent anisotropic features in previously published experimental data on fibroblasts, endothelial cells, and epithelial cells on adhesive micropatterned substrates. Our work highlights the role of cytoskeletal anisotropy in the generation of cellular traction forces, and provides a computational strategy for investigating stress fiber anisotropy in dynamical and multicellular settings. Author summaryCells that make up multicellular life perform a variety of mechanical tasks such as pulling on surrounding tissue to close a wound. The mechanisms by which cells perform these tasks are, however, incompletely understood. In order to better understand how they generate forces on their environment, cells are often studied in vitro on compliant substrates, which deform under the so called "traction forces" exerted by the cells. Mathematical models complement these experimental approaches because they help to interpret the experimental data, but most models for traction forces on adhesive substrates assume that cells contract isotropically, i.e., they do not contract in a specific direction. However, many cell types contain organized structures of stress fibers - strong contracting cables inside the cell - that enable cells to exert forces on their environment in specific directions only. Here we present a computational model that predicts both the orientations of these stress fibers as well as the forces that cells exert on the substrates. Our model reproduces both the orientations and magnitudes of previously reported experimental traction forces, and could serve as a starting point for exploring mechanical interactions in multicellular settings.

biophysics↗

Epithelia are multiscale active liquid crystals

Biological processes such as embryogenesis, wound healing and cancer progression, crucially rely on the ability of epithelial cells to coordinate their mechanical activity over length scales order of magnitudes larger than the typical cellular size. While regulated by signalling pathways, such as YAP (yes-associated protein), MAPK (mitogen-activated protein kinase) and Wnt, this behavior is believed to additionally hinge on a minimal toolkit of physical mechanisms, of which liquid crystal order is the most promising candidat. Yet, experimental and theoretical studies have given so far inconsistent results in this respect: whereas nematic order is often invoked in the interpretation of experimental data, computational models have instead suggested that hexatic order could in fact emerge in the biologically relevant region of parameter space. In this article we resolve this dilemma. Using a combination of in vitro experiments on Madin-Darby canine kidney cells (MDCK), numerical simulations and analytical work, we demonstrate that both nematic and hexatic order is in fact present in epithelial layers, with the former being dominant at large length scales and the latter at small length scales. In MDCK GII cells on uncoated glass, these different types of liquid crystal order crossover at 34 {micro}m, corresponding approximatively to clusters of 21 cells. Our work sheds light on the emergent organization of living matter, provides a new set of tools for analyzing the structure of epithelia and paves the way toward a comprehensive and predictive mesoscopic theory of tissues.

biophysics↗

Cellular geometry controls the efficiency of motile sperm aggregates

Teams of cooperating sperm have been found across several vertebrate and invertebrate species, ranging from sperm pairs to massive aggregates containing hundreds of cells. Although the biochemical mechanisms involved in sperm-sperm adhesion are unclear, aggregation can enhance the motility of the cells. Here, we report a thorough computational investigation on the role of cellular geometry in the performance of sperm aggregates. The sperm head is modeled as a persistent random walker characterized by a non-trivial three-dimensional shape and equipped with an adhesive region where cell-cell binding occurs. By considering both a simple parametric head shape and a computer reconstruction of a real head shape based on morphometric data, we demonstrate that the geometry of the head and the structure of the adhesive region crucially affect both the stability and motility of the aggregates. Our analysis further suggests that the apical hook, commonly found in the sperm of most muroid rodents, might serve to shield portions of the adhesive region and promote efficient alignment of the velocities of the interacting cells.

evolutionary biology↗