(451c) Can Cells Do Calculus? Curvature and Edges As Cues for Structure Formation within Cells

Geometry and confinement are powerful means of directing assembly in soft matter, and are widely exploited to organize systems ranging from colloidal suspensions to complex macromolecules. However, the importance of boundary geometry is less explored in biology, despite decades of research on cell patterns and their establishment during development and tissue morphogenesis. Here, we explore geometry as a cue for cell organization. In particular, we study how cells respond to curvatures and edges on a bounding surface. Surfaces with radii of curvature similar to the cell length can drive organization within cells and cell monolayers. Mouse embryonic fibroblasts and human vascular smooth muscle cells sense substrate curvature and organize their stress fibers in response to this cue. Furthermore, cells move differently on curved surfaces. On planar surfaces, cells typically migrate in the same direction as their ventral stress fibers. On curved surfaces, this relationship can be violated; cells can re-polarize and migrate orthogonally to these structures. Near edges, cells elongate and align. Within monolayers, cells form structures with nematic organization, with defects near corners related to the direction of cell migration. Open issues related to underlying mechanism and the potential utility of these observations in application are discussed. This research was performed by Nate Bade in collaboration with Randall Kamien and Richard Assoian.