Cells have evolved specific sensing mechanisms to recognize and integrate a diverse set of environmental cues. It is now well established that cells can detect sub-cellular topographical features, and these physical cues are sufficient to direct cell migration and trigger stem cell commitment to specific lineage. Nevertheless, most efforts in this field are focused on the impact of unnatural or geometric structures (e.g.: arrays of dots, microgrooves, micro pillars) and very little is known about natural and smooth cell-scale topographies, a ubiquitous trait of natural environments. Through this talk, recent findings that demonstrate that adherent cells can read and integrate cell-scale curvature variations will be presented. This new cellular sense was termed “curvotaxis”. We developed sinusoidal 3D surfaces presenting continuous variations of cell-scale curvature, and monitored cell behavior on these simplified biomimetic landscapes. We found that cells avoid convex regions during their migration and position themselves in concave valleys. Computational modeling, small-scale functional screen and live imaging suggest that curvotaxis relies on a dynamic interplay between the nucleus and the actin network - the nucleus acting as a mechano-sensing organelle that drives cell migration. Further analysis show that substratum concavity increases nuclear sphericity, lowers stress fiber tension and down-regulates a subset of genes involved in stem cell differentiation. Taken together, these data identify curvotaxis as a new guiding mechanism and suggest that cell-scale topography might be a true component of the stem cell niche. Keywords: surface topography, cell/surface interactions, curvature