Curated Optogenetic Publication Database

Abstract: In adherent cells, actomyosin contractility is regulated mainly by the RhoA signaling pathway, which can be controlled by optogenetics. To model the mechanochemical coupling in such systems, we introduce a finite element framework based on the discontinuous Galerkin method, which allows us to treat cell doublets, chains of cells, and monolayers within the same conceptual framework. While the adherent cell layer is modeled as an actively contracting viscoelastic solid on an elastic foundation, different models are considered for the Rho pathway, starting with a simple linear chain that can be solved analytically and later including direct feedback that can be solved only numerically. Our model predicts signal propagation as a function of coupling strength and viscoelastic timescales and identifies the conditions for optimal cell responses and wave propagation. In general, it provides a systematic understanding of how biochemistry and mechanics simultaneously contribute to the communication of adherent cells.

Abstract: Cell-generated forces play a major role in coordinating the large-scale behavior of cell assemblies, in particular during development, wound healing, and cancer. Mechanical signals propagate faster than biochemical signals, but can have similar effects, especially in epithelial tissues with strong cell-cell adhesion. However, a quantitative description of the transmission chain from force generation in a sender cell, force propagation across cell-cell boundaries, and the concomitant response of receiver cells is missing. For a quantitative analysis of this important situation, here we propose a minimal model system of two epithelial cells on an H-pattern ('cell doublet'). After optogenetically activating RhoA, a major regulator of cell contractility, in the sender cell, we measure the mechanical response of the receiver cell by traction force and monolayer stress microscopies. In general, we find that the receiver cells show an active response so that the cell doublet forms a coherent unit. However, force propagation and response of the receiver cell also strongly depend on the mechano-structural polarization in the cell assembly, which is controlled by cell-matrix adhesion to the adhesive micropattern. We find that the response of the receiver cell is stronger when the mechano-structural polarization axis is oriented perpendicular to the direction of force propagation, reminiscent of the Poisson effect in passive materials. We finally show that the same effects are at work in small tissues. Our work demonstrates that cellular organization and active mechanical response of a tissue are key to maintain signal strength and lead to the emergence of elasticity, which means that signals are not dissipated like in a viscous system, but can propagate over large distances.