Cell contact guidance via sensing anisotropy of network mechanical resistance
Greeshma Thrivikraman, Alicja Jagiełło, Victor K. Lai, Sandra L. Johnson, Mark Keating, Alexander T. Nelson, Billianne Schultz, Connie M. Wang, Alex J. Levine, Elliot L. Botvinick, Robert T. Tranquillo
Abstract
Significance Cell contact guidance in aligned fibers is, in many ways, a final frontier in directed cell migration. Despite its ubiquitous importance in normal/pathological processes, notably metastasis from solid tumors, and scaffold design for tissue engineering/regenerative medicine, the signal that induces contact guidance in an aligned fiber network has defied elucidation. We report definitive demonstration of a biophysical signal sensed by fibroblasts cultured within aligned fibrils: mechanical resistance anisotropy, the resistance resulting from viscous and elastic properties of fibril network to pseudopod protrusion/retraction and how it differs in different directions (anisotropy). This discovery is of fundamental importance to understanding contact guidance, providing a rationale, currently lacking, for future studies of the intracellular signal transduction/response pathways for physiologically relevant contact guidance.