In tissue, cells are living in a 3D environment. Like planets in space, cells are not floating around and freely moving. Their movement and general behavior are governed by a variety of physical interactions. At the cellular level, these interactions comprise of molecular forces mediated by the mechanical reciprocity between the cell and the surrounding environment. These phenomena play a key role in cell migration and development, tissue regeneration and homeostasis, and pathologic changes. Mechanical reciprocity between cells and their surroundings is mostly observed in natural extracellular matrix (ECM), like collagen and fibrin gels. Natural ECMs possess a fibrous structure and complex nonlinear mechanics, including the strain–stiffening behavior, time-dependent viscoelasticity, and mechanical plasticity. However, the lower tunability of their bio/mechanical properties hinders the systematic study of the role of nonlinear mechanics in cell-matrix physical interactions. Moreover, the high degradability of natural ECMs does not allow the discrimination between physical interactions and enzyme-related biochemically remodeling. A comprehensive understanding of the interactions at the cell-matrix interface would enable the rational design of the next generation of biomaterials, with the goal of matching tissue and ECM properties for the development of improved in vitro models, and wide applications in regenerative medicine and tissue engineering. In the project, we combed a fibrous synthetic material with unique mechanical properties and advanced fluorescence microscopy techniques to investigate how cellular forces are related to the mechanical properties of the matrix, and how these affect cellular behavior.
