Non-Linear Mechanical Response Transforms a Graded Molecular Distribution into a Step-Wise Output in Cell Behavior

Abstract

The intrinsic genetic programme of a cell is not always sufficient to explain the cell's activities. External mechanical stimuli are increasingly being recognized as determinants of cell behavior. In the epithelial folding event that constitutes the beginning of gastrulation in Drosophila, the genetic programme of the future mesoderm leads to the establishment of a contractile actomyosin network that triggers apical constriction of cells, and thereby, furrow formation. However, some cells do not constrict but instead stretch, even though they share the same genetic programme as their constricting neighbors. We show here that tissue-wide interactions override the intrinsic programme of a subset of cells, forcing them to expand even when an otherwise sufficient amount and concentration of apical, active actomyosin has been accumulated. Models based on contractile forces and linear stress-strain responses are not sufficient to reproduce experimental observations, but simulations in which cells behave as materials with non-linear mechanical properties do. Our models also show that this behavior is an emergent property of supracellular actomyosin networks, in accordance with our experimental observations of actin reorganization within streching cells, with this event being stochastic and rare in cells with high myosin levels, but reproducible in cells with lower concentrations.