Proc. Natl Acad. Sci. USA 108, 16565–16570 (2011)

Credit: © 2011 NAS

Cells in contact with surfaces typically respond to their micro- and nanostructure, for example by spreading, changing the degree of adhesion, or differentiating. However, the mechanisms by which surface topography elicits specific cellular responses are not well understood, and therefore it is generally not possible to predict which feature sizes and shapes would be optimal to evoke a specific cell action. A team of researchers in the Netherlands have applied a brute-force, combinatorial approach to screen for unique surface topologies that induce desired cellular responses. By using a mathematical algorithm that combines a few primitive shapes, the researchers generated an enormously large library of topographic features and randomly selected 2,176 of them, which were photolithographically moulded in silicon and then imprinted in poly(DL-lactic acid) films. After seeding human mesenchymal stromal cells on the films, the team found that the cells' proliferation correlated with the Fourier parameters of certain surface features. High-throughput technologies that screen for surface topography and material composition should speed up the decoding of cell–topography and cell–material interactions.