Static mechanical stretch induces collective alignment of C2C12 myoblasts

Area of Science:

• Mechanobiology
• Tissue Engineering
• Biophysics

Background:

• Cell alignment is crucial for tissue development and function.
• Mechanisms driving density-dependent collective cell alignment are not fully understood.

Purpose of the Study:

• To investigate the mechanisms of density-dependent collective cell alignment induced by mechanical stretch.
• To elucidate the roles of cellular forces and cell-cell interactions in maintaining cell order.

Main Methods:

• Utilized C2C12 myoblasts cultured under static uniaxial mechanical stretch.
• Observed alignment in cultures of varying cell densities.
• Employed coarse-grained agent-based simulations.
• Distinguished between passive substrate deformation and active cell-mediated processes.

Main Results:

• Mechanical stretch induced collective cell alignment in a density-dependent manner.
• Alignment occurred in two phases: a passive phase driven by substrate deformation and an active phase dependent on cell density.
• High-density cultures maintained alignment through cell-cell interactions, while low-density cultures showed alignment dissipation.
• Agent-based simulations supported the roles of self-generated cellular forces and intercellular interactions in stabilizing alignment.

Conclusions:

• Cell-cell interactions are critical for stabilizing collective cell alignment in response to mechanical cues.
• A combination of cellular forces and intercellular interactions orchestrates multicellular ordering.
• Findings offer insights into the mechanobiology of tissue morphogenesis and provide design principles for tissue engineering.