Curvature Perception of Mesenchymal Cells on Mesoscale Topographies

Cells can sense geometrical cues with sizes of several tens of micrometers in their vicinity. Recent in vitro studies show that cells can adapt their shape, align along specific directions, or regulate other cellular functions when grown on surfaces with curvatures larger than their size. Although possible mechanisms for such responses like the alignment along axial cues have been suggested, a detailed understanding of the involved cellular processes remains open. This work addresses this gap by systematically investigating mesenchymal cell and nucleus orientation responses using a low-cost model surface platform, the CurvChip. Using an array of cylindrically curved topographies with radii of curvatures ranging from tens to hundreds of micrometers, the contact guidance response of cells and nuclei is quantified in dependence on substratum curvature and manipulation of cytoskeletal components. Results suggest a desired perceived curvature for the investigated cells, and a very sensitive and robust curvature perception mechanism, as the effect of pharmacological manipulation of cytoskeletal components is relatively small. Furthermore, a comparison with previously published work strengthens the hypothesis of an involvement of the nucleus in the cell response to three-dimensional (3D) curvatures.