We propose a minimal mathematical model to explain long-range coordination of dynamics of multiple cells in epithelial spreading, which may be induced, under different conditions, by a chemical signal, or mechanical stress, or both. The model is based on chemo-mechanical interactions including a chemical effect of stress and concentration-dependent traction. The results, showing kinase concentration distribution and cell displacement, allow us to reproduce two activation waves on different time scales observed in the experiment, and distinguish between distinct dynamical patterns observed under conditions of injury or unconstraining.
Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the Enveloping Cell Layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish epiboly. The control of EVL cell-division orientation by tension involves cell elongation and requires my…
In living matter, shape fluctuations induced by acto-myosin are usually studied in vitro via reconstituted gels, whose properties are controlled by changing the concentrations of actin, myosin and cross-linkers. Such an approach deliberately avoids to consider the complexity of biochemical signaling inherent to living systems. Acto-myosin activity inside living cells is mainly regulated by the Rho signaling pathway which is composed of multiple layers of coupled activators and inhibitors. We investigate how such a pathway controls the dynamics of confluent epithelial tissues by tracking the di…
We found evidence of dynamic scaling in the spreading of MDCK monolayer, which can be characterized by the Hurst exponent $α = 0.86$ and the growth exponent $β = 0.73$, and theoretically and experimentally clarified the mechanism that governs the contour shape dynamics. During the spreading of the monolayer, it is known that so-called "leader cells" generate the driving force and lead the other cells. Our time-lapse observations of cell behavior showed that these leader cells appeared at the early stage of the spreading, and formed the monolayer protrusion. Informed by these observations, we d…
Cell shape is determined by a balance of intrinsic properties of the cell as well as its mechanochemical environment. Inhomogeneous shape changes underly many morphogenetic events and involve spatial gradients in active cellular forces induced by complex chemical signaling. Here, we introduce a mechanochemical model based on the notion that cell shape changes may be induced by external diffusible biomolecules that influence cellular contractility (or equivalently, adhesions) in a concentration-dependent manner -- and whose spatial profile in turn is affected by cell shape. We map out theoretic…
During the spreading of epithelial tissues, the advancing tissue front often develops fingerlike protrusions. Their resemblance to traditional viscous fingering patterns in driven fluids suggests that epithelial fingers could arise from an interfacial instability. However, the existence and physical mechanism of such a putative instability remain unclear. Here, based on an active polar fluid model for epithelial spreading, we analytically predict a generic instability of the tissue front. On the one hand, active cellular traction forces impose a velocity gradient that leads to an accelerated f…
Collective cell migration plays a crucial role in many developmental processes that underlie morphogenesis, wound healing, or cancer progression. In such coordinated behaviours, cells are organised in coherent structures and actively migrate to serve different biological purposes. In some contexts, namely during epithelial wound healing, it is well known that a migrating free-edge monolayer develops finger-like instabilities, yet the onset is still under debate. Here, by means of theory and numerical simulations, we shed light on the main mechanisms driving the instability process, analysing t…
Morphogenesis, tissue regeneration and cancer invasion involve transitions in tissue morphology. These transitions, caused by collective cell migration (CCM), have been interpreted as active wetting/de-wetting transitions. This phenomenon is considered on model system such as wetting of cell aggregate on rigid substrate which includes cell aggregate movement and isotropic/anisotropic spreading of cell monolayer around the aggregate depending on the substrate rigidity and aggregate size. This model system accounts for the transition between 3D epithelial aggregate and 2D cell monolayer as a pro…
Centro de Física Teórica e Computacional, Faculdade de Ciências da Universidade de Lisboa（里斯本大学理学院理论物理与计算中心）；Departamento de Física, Faculdade de Ciências da Universidade de Lisboa（里斯本大学理学院物理系）；Departamento de Física, Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa（里斯本理工学院里斯本高等工程学院物理系）
Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between 2D epithelial monolayers and 3D spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phe…
Many bacterial species exchange signaling molecules to coordinate population-wide responses. For this process known as quorum sensing the concentration of the respective molecules is crucial. Here we consider the interaction between spatially distributed bacterial colonies so that the spreading of the signaling molecules in space becomes important. The exponential growth of the signal-producing populations and the corresponding increase in signaling molecule production result in an exponential concentration profile that spreads with uniform speed. The theoretical predictions are supported by e…
Many types of motile cells perform durotaxis, namely, directed migration following gradients of substrate stiffness. Recent experiments have revealed that cell monolayers can migrate toward stiffer regions even when individual cells do not -- a phenomenon known as collective durotaxis. Here we address the spontaneous motion of finite cohesive cell monolayers on a stiffness gradient. We theoretically analyze a continuum active polar fluid model that has been tested in recent wetting assays of epithelial tissues, and includes two types of active forces (cell-substrate traction and cell-cell cont…
Center for Quantitative Biology（定量生物学中心）；Peking-Tsinghua Joint Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China（北京大学-清华联合生命科学中心，先进跨学科研究学院，北京大学，北京，中国）；James Franck Institute（詹姆斯·弗兰克研究所）；Department of Physics, The University of Chicago, Chicago, Illinois 60637, USA（芝加哥大学物理系，芝加哥，伊利诺伊州，60637，美国）；Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA（西北大学费因伯格医学院，芝加哥，伊利诺伊州，60611，美国）；Gulliver, ESPCI Paris, Université PSL, CNRS, 75005 Paris, France（古利弗，巴黎ESPCI，巴黎综合理工学院，CNRS，巴黎，法国）；Cell Biology, The University of Chicago, Chicago, Illinois, 60637, USA（细胞生物学，芝加哥大学，芝加哥，伊利诺伊州，60637，美国）；Pritzker School of Molecular Engineering, The University of Chicago, Chicago, Illinois, 60637, USA（普里茨克分子工程学院，芝加哥大学，芝加哥，伊利诺伊州，60637，美国）；Leinweber Institute for Theoretical Physics, University of Chicago, Chicago, Illinois 60637, USA（莱因韦伯理论物理学研究所，芝加哥大学，芝加哥，伊利诺伊州，60637，美国）
Many motile biological cells navigate along concentration gradients of signaling molecules: This chemotaxis guides for instance sperm cells from marine invertebrates, which have to find egg cells in the ocean. While chemotaxis has been intensively studied for idealized conditions of rotationally symmetric gradients in still water, natural gradients are usually distorted, e.g., by turbulent flows in the ocean. Recent experiments and direct numerical simulations with sperm cells and bacteria surprisingly suggest the existence of an optimal flow strength at which chemotaxis is more effective than…
