New depths in cell behaviour: reactions of cells to nanotopography.

The physical and molecular biological bases of the reactions of cells to features of the topography of the substratum or environment on which and in which cells live, both in culture and in the embryo, are discussed. The fact that most, if not all, cells react to micrometric and nanometric topography is stressed. Some cell types will react to steps as shallow as 11 nm. Methods of fabricating such topographies in a variety of materials are outlined. Types of topography and the reactions of cells to these are described. It is emphasized that different cell types are sensitive to fairly specific ranges of size of topography. Reactions to topography include cell orientation, changes in cell motility, cell adhesion and cell shape. The term 'contact guidance' has been used in this field, but the term 'topographic reaction' is more appropriate, since it covers the wide range of reactions that are reported. In addition, the reactions involve activation of tyrosine kinases, cytoskeletal condensation and further downstream activation and inactivation of gene expression. The reactions to topography are probably due to stretch reactions of the cells to the substratum and not to chemical details of the substratum. The reasons for this are that a given cell type reacts in much the same way to the same topography made with different materials and that, when both chemical patterns and topographic ones are offered to cells, topography tends to have a greater effect than chemical patterns.