Protrusions at the leading-edge of a cell play an important role in sensing the extracellular cues, during cellular spreading and motility. Recent studies provided indications that these protrusions wrap (coil) around the extra-cellular fibers. The details of this coiling process, and the mechanisms that drive it, are not well understood. We present a combined theoretical and experimental study of the coiling of cellular protrusions on fibers of different geometry. Our theoretical model describes membrane protrusions that are produced by curved membrane proteins that recruit the protrusive forces of actin polymerization, and identifies the role of bending and adhesion energies in orienting the leading-edges of the protrusions along the azimuthal (coiling) direction. Our model predicts that the cell’s leading-edge coils on round fibers, but the coiling ceases for a fiber of elliptical (flat) cross-section. These predictions are verified by 3D visualization and quantitation of coiling on suspended fibers using Dual-View light-sheet microscopy (diSPIM). Overall, we provide a theoretical framework supported by high spatiotemporal resolution experiments capable of resolving coiling of cellular protrusions around extracellular fibers of varying diameters. Significance Statement Cells adhere and migrate in environments that are composed of fibrous structures, such as the thin filaments of the extracellular matrix, or the wider axons and dendrites of neurons. In recent experiments, cells have been observed to form leading edge protrusions on such surfaces, that seem to coil around the extracellular fibers. However, the mechanism responsible for the formation of such coiling protrusions is not understood. Here, we provide a combined experimental and theoretical approach to explain the emergence of coiling protrusions. Our model is based on the self-organization of curved proteins that recruit actin polymerization at the leading edge of the cell, when spreading over an adhesive fiber.

Coiling of cellular protrusions around extracellular fibers