Extracellular and intercellular force distribution in circularly shaped epithelia

Stress homeostasis in multicellular organisms is essential to tissue growth, development, and repair. However, how cellular forces are generated and transmitted within a multicellular organism to maintain stress homeostasis remains poorly understood. Here we employ cellular force microscopies to quantify extracellular traction and intercellular tension of circularly shaped cohesive epithelia seeded on hydrogels of various stiffness. Our experimental measurements show that the traction force is both colony size and gel stiffness dependent. A minimal mechanics model is developed and predicts exponential decay of extracellular traction from the periphery to the center of the epithelial monolayers, which agrees with the experimental data. Our modeling analyses further show that the colony size and gel stiffness dependent traction is originated from the line tension effect and stiffness-dependent cell contractility, respectively. Our study lays down a foundation for future modeling and experimental measurements of cellular force generation, transmission, and distribution in multicellular organisms, which is critical to mechanobiological understanding of normal and disease development.