Left-right asymmetry in cell orientation requires high substrate rigidity

Left-right (LR) asymmetry in cell orientation is known as a result of intracellular events such as cytoskeletal organization. However, the dependence of LR asymmetry on mechanical properties of surrounding microenvironment has been unknown. Here we show that the cellular LR behavior was altered when cultured on extracellular matrix with varied substrate rigidity. Using micro-patterned substrate with high rigidity, we found that mouse fibroblasts exhibited a rotational alignment that has significant LR bias, and this LR bias can propagate from the edge to the center of cells. However, when cultured on soft substrate, the LR bias in cell orientation was lost. This finding suggests the importance of combining both intracellular and environment factors when guiding tissue formation, with implication for rebuilding damaged tissue for regenerative medicine.