Cellular Mechanics of Finger-Like Structures of Collective Cell Migration

Abstract

Finger-like structures emerging from groups of cells at the forefront of cell layer take crucial roles in the migration of collective cell assemblies. However, the mechanics of the finger-like structure has not been fully understood. Here, we constructed a two-dimensional collective cell migration model and quantitatively analyzed the cellular mechanics of finger-like structures during the collective cell migration through experimental study and numerical simulation. We found that substrate stiffness, cell density, cell prestress, and mechanical loading significantly influence the generation and behaviors of the finger-like structures by regulating the lamellipodia spreading area, cellular traction force, and collectivity of cell motion. We showed that the regions with higher maximum principal stress tend to produce larger finger-like structures. Increasing the spreading area of lamellipodia and the velocity of leader cells could promote the generation of higher finger-like structures. For a quantitative understanding of the mechanisms of the effects of these mechanical factors, we adopted a coarse-grained cell model based on the traction-distance law. Our numerical simulation recapitulated the cell velocity distribution, cell motility integrity, cell polarization, and stress distribution in the cell layer observed in the experiment. These analyses revealed the cellular mechanics of the finger-like structure and its roles in collective cell migration. This study provides valuable insights into the collective cell behaviors in tissue engineering and regenerative medicine for biomedical applications.