The Effect of Substrate Stiffness on Elastic Force Transmission in the Epithelial Monolayers over Short Timescales

Abstract Purpose The importance of mechanical forces and microenvironment in guiding cellular behavior has been widely accepted. Together with the extracellular matrix (ECM), epithelial cells form a highly connected system subjected to various cues from their environment, such as ECM stiffness, tensile compressive forces. stiffness linked many pathologies, including tumor formation. However, our understanding effect its heterogeneities on rapid force transduction multicellular systems not fully addressed. Methods We used experimental computational methods. Epithelial were cultured elastic hydrogels fluorescent nanoparticles. Single moved by micromanipulator, epithelium substrate deformation recorded. developed model replicate experiments quantify distribution epithelium. Our further enabled simulations local gradients. Results found that affects following an external force. Also, results indicate heterogeneities, e.g., gradients, can substantially influence strain redistribution cell monolayers. Furthermore, we cells’ apico-basal elasticity provides level isolation between apical cell–cell junctions basal focal adhesions. Conclusions simulation show increased due tumor, mechanically isolate modulate signaling over distances. potential facilitate future studies interactions monolayers substrates.