Dynamically Re‐Organized Collagen Fiber Bundles Transmit Mechanical Signals and Induce Strongly Correlated Cell Migration and Self‐Organization

Correlated cell migration in fibrous extracellular matrix (ECM) is important in many biological processes. During migration, cells can remodel the ECM, leading to the formation of mesoscale structures such as fiber bundles. However, how such mesoscale structures regulate correlated single‐cells migration remains to be elucidated. Here, using a quasi‐3D in vitro model, we investigate how collagen fiber bundles are dynamically re‐organized and guide cell migration. By combining laser ablation technique with 3D tracking and active‐particle simulations, we definitively show that only the re‐organized fiber bundles that carry significant tensile forces can guide strongly correlated cell migration, providing for the first time a direct experimental evidence supporting that matrix‐transmitted long‐range forces can regulate cell migration and self‐organization. This force regulation mechanism can provide new insights for studies on cellular dynamics, fabrication or selection of biomedical materials in tissue repairing, and many other biomedical applications. Collagen fibers are dynamically re‐organized by cells, and are able to transmit tensile force for precise cell‐communication at single‐cells level. This mechanism also explains the self‐organization of multiple cells in the quasi‐3D microenvironment.