Cells have evolved multiple mechanisms to apprehend and adapt finely to their environment. Here we report a new cellular ability, which we term “curvotaxis” that enables the cells to respond to cell-scale curvature variations, a ubiquitous trait of cellular biotopes. We develop ultra-smooth sinusoidal surfaces presenting modulations of curvature in all directions, and monitor cell behavior on these topographic landscapes. We show that adherent cells avoid convex regions during their migration and position themselves in concave valleys. Live imaging combined with functional analysis shows that curvotaxis relies on a dynamic interplay between the nucleus and the cytoskeleton—the nucleus acting as a mechanical sensor that leads the migrating cell toward concave curvatures. Further analyses show that substratum curvature affects focal adhesions organization and dynamics, nuclear shape, and gene expression. Altogether, this work identifies curvotaxis as a new cellular guiding mechanism and promotes cell-scale curvature as an essential physical cue.
We quantitatively evaluated the adhesion of human osteoblasts on orthopedic metallic substrates (Ti6Al4V alloy) with various surface roughnesses at several times after inoculation and studied its correlation with qualitative changes in the expression of adhesion proteins and with parameters extensively describing the surface topographies. Cells were orientated in a parallel order on polished surfaces. This orientation was not affected by residual grooves after polishing. On sandblasted surfaces the cells never attained confluence and had a stellate shape, and the cell layer had no particular organization. Extracellular matrix (fibronectin, type I collagen, osteopontin) and cytoskeletal protein (actin, vinculin) orientation reflected the cell layer organization. In our experiment human osteoblasts expressed alpha3beta1 integrin but not alpha2beta1 integrin. In addition to currently analyzed roughness magnitude parameters, we calculated roughness organization parameters (fractal dimension parameters) of the substrates. We observed lower adhesion and proliferation on less organized surfaces (i.e., sandblasted ones). The significant statistical correlation observed between fractal dimension parameters (describing surface roughness organization) and cell parameters adds a new concept to the studies of substratum roughness influence on cell behavior. An attempt at modelization of the cell-surface interaction was made that includes the influence of fractal dimensions parameters.
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