Nanotopography controls single-molecule mobility to determine overall cell fate

Abstract

The addition of nanoscale distortion to ordered nanotopographies consistently determines an osteogenic fate in stem cells. Although disordered and ordered nanopit arrays have identical surface areas, array symmetry has opposite effects on cell fate. We aimed to understand how cells sense disorder at the nanoscale. We observed effects in the early formation of cell and focal adhesions that controlled long-term cell fate. Disordered nanopits consistently yielded larger focal adhesions at a faster rate, prompting us to investigate this at the molecular scale. Super-resolution microscopy revealed that the nanopits did not act as nucleation points, as previously thought. Rather, nanopit arrays altered the plasma membrane and acted as barriers that changed molecular diffusion. The local areas corralled by four nanopits were the smallest structures that exerted diverging effects between ordered and disordered arrays. Heterogeneity in the local area on disordered arrays increased the proportion of fastest and slowest diffusing molecules. This resulted in higher quantity, more frequent formation and clustered arrangement of nascent adhesions, i.e., the modular units on which focal adhesions are built. This work presents a new pathway to exploit nanoscale sensing to dictate cell fate.

Controlled Metal Crumpling as an Alternative to Folding for the Fabrication of Nanopatterned Meta-Biomaterials

“…Similar observations have been made in previous studies [3] and suggest that the effects of the different adaptation of cells to bTi nanopatterns go beyond morphological changes and involve cell metabolism. It has been shown that surface nanotopography affects the molecular diffusion through the cell plasma membrane [52] and furthermore, cell mechanics and metabolism are mutually related [53]. Therefore, further dedicated metabolic studies are required to understand why cells may show lower levels of metabolic activity when cultured on nanopatterned structures.…”