RESUMO
Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity.
Assuntos
Movimento Celular/fisiologia , Polaridade Celular/fisiologia , Modelos Biológicos , Resinas Acrílicas , Animais , Butadienos/farmacologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Contagem de Células , Técnicas de Cultura de Células , Movimento Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Tamanho Celular , Colágeno Tipo I/metabolismo , Cães , Módulo de Elasticidade , Inibidores Enzimáticos/farmacologia , Fator de Crescimento Epidérmico/farmacologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Células Madin Darby de Rim Canino , Microscopia de Fluorescência , Nitrilas/farmacologia , Periodicidade , Propriedades de SuperfícieRESUMO
Coordinated motion of cell monolayers during epithelial wound healing and tissue morphogenesis involves mechanical stress generation. Here we propose a model for the dynamics of epithelial expansion that couples mechanical deformations in the tissue to contractile activity and polarization in the cells. A new ingredient of our model is a feedback between local strain, polarization, and contractility that naturally yields a mechanism for viscoelasticity and effective inertia in the cell monolayer. Using a combination of analytical and numerical techniques, we demonstrate that our model quantitatively reproduces many experimental findings [Nat. Phys. 8, 628 (2012)], including the buildup of intercellular stresses, and the existence of traveling mechanical waves guiding the oscillatory monolayer expansion.
