Topographic Cues Guiding Cell Polarization via Distinct Cellular Mechanosensing Pathways

Abstract Cell polarization exists in a variety of tissues to regulate cell behaviors and functions. Space constraint (spatially limiting cell extension) and adhesion induction (guiding adhesome growth) are two main ways to induce cell polarization according to the microenvironment topographies. However, the mechanism of cell polarization induced by these two ways and the downstream effects on cell functions are yet to be understood. Here, space constraint and adhesion induction guiding cell polarization are achieved by substrate groove arrays in micro and nano size, respectively. Although the morphology of polarized cells is similar on both structures, the signaling pathways to induce the cell polarization and the downstream functions are distinctly different. The adhesion induction (nano‐groove) leads to the formation of focal adhesions and activates the RhoA/ROCK pathway to enhance the myosin‐based intracellular force, while the space constraint (micro‐groove) only activates the formation of pseudopodia. The enhanced intracellular force caused by adhesion induction inhibits the chromatin condensation, which promotes the osteogenic differentiation of stem cells. This study presents an overview of cell polarization and mechanosensing at biointerface to aid in the design of novel biomaterials.