Analysis of the mechanical characteristics of collective skeletal muscle cell migration upon the biochemical environment of injured muscle.

Abstract

Skeletal muscle tissues inherently contain undifferentiated myoblasts and satellite cells, providing sources for self-regeneration following the injury. Muscle regeneration requires collective migration of constituent cells toward the injured sites, while muscle differentiation also requires collective migration for proper alignment. Despite the importance of the collective behavior of muscle cells, most studies on muscle cell motility during skeletal muscle regeneration involve single-cell behavior, and little is known about the collective behavior. In this study, we constructed an in vitro cell-based platform to model skeletal muscles with specific biomolecules released from the skeletal muscle cells using conditioned media from the normal versus injured culture conditions. We measured the migration behavior and the mechanical characteristics of the cell clusters represented by the traction force and intercellular stress under different media conditions. We then identified that the heterogeneous population of skeletal muscle cell clusters exhibited distinct collective migration patterns in the injury-mimicking state compared to the normal-mimicking condition. Furthermore, the traction and stress maps of the migrating cells also showed uniquely different patterns in each media condition and were closely related to the migrating behaviors. These results suggest that the selective activation of specific cells in the migrating clusters by the biochemical cues from the normal and injured skeletal muscles can induce these distinct migrating patterns and mechanical characteristics.