The Yin-Yang of Rigidity Sensing: How Forces and Mechanical Properties Regulate the Cellular Response to Materials

According to the Chinese yin-yang concept, seemingly opposing forces give rise and respond to each other. Opposing forces, whether passive or active, are also at work when cells adhere to a substrate or extracellular matrix, sense environmental properties, and finally respond to them. In this review, we describe molecular elements inside and outside of the cell that establish labile physical connections, and how forces regulate their interplay, namely formation, reinforcement, breakage, and reconfiguration of these elements. What a cell locally feels thus depends not only on the displacement of materials, but also on the stability of molecular interactions, on the conversion of mechanical forces to biochemical signals by stretching proteins into structural intermediates (mechano-chemical signal conversion), and on the micro- and nanoscopic features of the extracellular material. Current methodologies for quantifying forces in the cellular context at different length scales are also critically assessed.