The development of novel biomaterials able to control cell activities and direct their fate is warranted for engineering functional biological tissues, advanced cell culture systems, single-cell diagnosis as well as for cell sorting and differentiation. It is well established that crosstalk at the cell–material interface occurs and this has a profound influence on cell behaviour. However, the complete deciphering of the cell–material communication code is still far away. A variety of material surface properties have been reported to affect the strength and the nature of the cell–material interactions, including biological cues, topography and mechanical properties. Novel experimental evidence bears out the hypothesis that these three different signals participate in the same material–cytoskeleton crosstalk pathway via adhesion plaque formation dynamics. In this review, we present the relevant findings on material-induced cell response along with the description of cell behaviour when exposed to arrays of signals—biochemical, topographical and mechanical. Finally, with the aid of literature data, we attempt to draw unifying elements of the material–cytoskeleton–cell fate chain.

Topographic patterns are known to affect cellular processes such as adhesion, migration and differentiation. However, the optimal way to deliver topographic signals to provide cells with precise instructions has not been defined yet. In this work, we hypothesize that topographic patterns may be able to control the sensing and adhesion machinery of cells when their interval features are tuned on the characteristic lengths of filopodial probing and focal adhesions (FAs). Features separated by distance beyond the length of filopodia cannot be readily perceived; therefore, the formation of new adhesions is discouraged. If, however, topographic features are separated by a distance within the reach of filopodia extension, cells can establish contact between adjacent topographic islands. In the latter case, cell adhesion and polarization rely upon the growth of FAs occurring on a specific length scale that depends on the chemical properties of the surface. Topographic patterns and chemical properties may interfere with the growth of FAs, thus making adhesions unstable. To test this hypothesis, we fabricated different micropatterned surfaces displaying feature dimensions and adhesive properties able to interfere with the filopodial sensing and the adhesion maturation, selectively. Our data demonstrate that it is possible to exert a potent control on cell adhesion, elongation and migration by tuning topographic features’ dimensions and surface chemistry.