Nanotopography sensing through intracellular signaling and mechanotransduction with an emphasis on bone

Synthetic substrates have demonstrated efficacy over numerous cell phenotypes from morphology to proliferation and differentiation. This becomes especially true when the substrate's topography approaches the nanoscale. Nanotopography, structures ranging from 101 nm-103 nm as defined in the context of this review, can have a significant impact on cell signaling. The signaling mechanisms that are impacted by nanotopography are described within this article. Background material on nanotopography and mechanobiology will be briefly discussed, followed by a detailed discussion of the membrane-related signaling mechanisms, specifically, mechanisms related to membrane stretching, growth factors, ions, and curvature sensing. The role of cell-surface and cell-cell anchoring proteins, integrins and cadherins respectively, in topography sensing is discussed with respect to their ability to act as topography sensors. Developing an understanding of nanotopography's ability to influence cell signaling leading to phenotype shift is of great importance because it enables development of future generations of biomaterial substrates capable of targeted control over cellular signaling leading to directed cell phenotype.