Molecular clutch model-inspired design of dynamic mechanical hydrogels for extracellular matrix mimicry

Originally developed to explain integrin-mediated adhesion on static substrates, the molecular clutch model now serves as a framework that links substrate relaxation to force transmission, adhesion reinforcement, and downstream signaling via clutch-like engagement between actin fibers and the extracellular matrix (ECM). Hydrogels serve as ideal materials for mimicking the native ECM. This review systematically presents strategies for endowing materials with targeted dynamic mechanical behaviors and for constructing adhesive interfaces, aiming to better replicate the key dynamic mechanical characteristics of the cellular microenvironment and expand hydrogel applications in biomedicine. Extending the molecular clutch model provides a theoretical tool for studying cellular mechanobiological responses in tissues, thereby facilitating the translation of biomechanical discoveries into material design principles. This integration opens new avenues for designing cellular microenvironments with complex mechanical properties that more closely approximate physiological conditions, providing a novel perspective for research across mechanobiology, biomaterials, and mechanomedicine.