Micromechanical Design Criteria for Tissue Engineering Biomaterials

A key goal in the field of tissue engineering is the development of novel biomimetic materials that mimic the features of natural materials responsible for normal control of multicellular assembly, and seamlessly integrate with living tissues. Past work in this area has focused on the optimization of biomaterial chemistry and selection of appropriate biological cues (e.g., morphogens, ECM-derived adhesive ligands) to promote effective tissue development. However, tissue formation is also influenced by microscale mechanical forces that cells generate in their contractile cytoskeleton and exert on their adhesions to extracellular matrix (ECM) and to neighboring cells. Cells also sense these forces through transmembrane adhesion receptors, such as integrins and cadherins, which focus mechanical stresses on load-bearing molecular structures within membrane adhesion complexes (e.g., focal adhesions and junctional complexes) and linked cytoskeletal filaments and nuclear scaffolds. Resulting stress-induced changes in molecular shape and function mediate mechanotransduction – the conversion of a mechanical signal into an intracellular biochemical response – ultimately leading to integrated changes in global cell behavior that drive tissue patterning. Here, we highlight the key role that mechanical forces play in tissue development, and discuss how this knowledge might be leveraged to create a new set of physical design criteria for the development of novel biomimetic materials for regenerative medicine.