Monolayer force generation and transmission is dictated by focal adhesion distribution

Abstract

For tissues to develop and maintain their function, cells must orchestrate their behaviour by generating and transmitting contractile forces. These forces are transmitted to their surrounding matrix or neighbouring cells via adhesion complexes. How tissues reach a force-balance is often assumed to involve intercellular stresses counterbalancing those in the substrate. However, experimental findings indicate that dampening focal adhesions can increase intercellular stresses. As the ECM is rarely uniform in composition or mechanical properties, it is important to understand how focal adhesions alter stress transmission and the force-balance of a tissue. To address this, we confined monolayers on disk or ring adhesive patterns to alter how they were bound to the substrate. Traction force microscopy and laser ablations of cell-cell junctions were used to examine stresses across epithelial monolayers whilst modulating substrate stiffness. We show that monolayers reach different force-balance states depending on focal adhesion distribution, with intercellular stresses not correlated with overall traction stresses on rings. Using an active matter model to examine the force-balance dynamics, we reveal that tissues reach a force-balance by generating non-uniform patterns of contractility linked to adhesion patterning. This work highlights the importance of considering the position and mechanical properties of cell-ECM and cell-cell attachments to capture the mechanical landscape of living tissues.