Cell sensing of physical properties at the nanoscale: Mechanisms and control of cell adhesion and phenotype.

The chemistry, geometry, topography and mechanical properties of biomaterials modulate biochemical signals (in particular ligand-receptor binding events) that control cells-matrix interactions. In turn, the regulation of cell adhesion by the biochemical and physical properties of the matrix controls cell phenotypes such as proliferation, motility and differentiation. In particular, nanoscale geometrical, topographical and mechanical properties of biomaterials are essential to achieve control of the cell-biomaterials interface. The design of such nanoscale architectures and platforms requires understanding the molecular mechanisms underlying adhesion formation and the assembly of the actin cytoskeleton. This review presents some of the important molecular mechanisms underlying cell adhesion to biomaterials mediated by integrins and discusses the nanoscale engineered platforms used to control these processes. Such nanoscale understanding of the cell-biomaterials interface offers exciting opportunities for the design of biomaterials and their application to the field of tissue engineering. STATEMENT OF SIGNIFICANCE: Biomaterials design is important in the fields of regenerative medicine and tissue engineering, in particular to allow the long term expansion of stem cells and the engineering of scaffolds for tissue regeneration. Cell adhesion to biomaterials often plays a central role in regulating cell phenotype. It is emerging that physical properties of biomaterials, and more generally the microenvironment, regulate such behaviour. In particular, cells respond to nanoscale physical properties of their matrix. Understanding how such nanoscale physical properties control cell adhesion is therefore essential for biomaterials design. To this aim, a deeper understanding of molecular processes controlling cell adhesion, but also a greater control of matrix engineering is required. Such multidisciplinary approaches shed light on some of the fundamental mechanisms via which cell adhesions sense their nanoscale physical environment.