Self‐Strengthening Adhesive Force Promotes Cell Mechanotransduction

Abstract The extracellular matrix (ECM) undergoes dynamic remodeling and progressive stiffening during tissue regeneration and disease progression. However, most of the artificial ECMs and in vitro disease models are mechanically static. Here, a self‐strengthening polymer coating mimicking the dynamic nature of native ECM is designed to study the cellular response to dynamic biophysical cues and promote cell mechanical sensitive response. Spiropyran (SP) is utilized as dynamic anchor group to regulate the strength of cell adhesive peptide ligands. Benefiting from spontaneous thermal merocyanine‐to‐spiropyran (MC–SP) isomerization, the resulting self‐responsive coating displays dynamic self‐strengthening of interfacial interactions. Comparing with the static and all of the previous dynamic artificial ECMs, cells on this self‐responsive surface remodel the weakly bonded MC‐based coatings to activate α5β1 integrin and Rac signaling in the early adhesion stage. The subsequent MC‐to‐SP conversion strengthens the ligand–integrin interaction to further activate αvβ3 integrin and RhoA/ROCK signaling in the latter stage. This sequential process enhances cellular mechanotransduction as well as the osteogenic differentiation of mesenchymal stem cells (MSCs). It is worth emphasizing that the self‐strengthening occurs spontaneously in the absence of any stimulus, making it especially useful for implanted scaffolds in regenerative medicine.