Actomyosin contractility as a mechanical checkpoint for cell state transitions.

Area of Science:

• Cell biology
• Mechanobiology
• Biophysics

Background:

• Cell state transitions create diverse cell populations.
• Origins of cell heterogeneity are often linked to gene regulation.
• The role of intrinsic cell mechanics in cell fate is largely unexplored.

Purpose of the Study:

• Investigate the contribution of cell mechanical properties to cell state heterogeneity.
• Determine the role of actomyosin contractile forces in cell fate decisions.
• Identify mechanical checkpoints influencing cell state transitions.

Main Methods:

• Utilized a single-cell platform to induce and study cell-state transitions.
• Performed temporal analysis of fibroblast colony morphology under lateral confinement.
• Employed unsupervised diffusion analysis to construct pseudo-trajectories of cell morphology.
• Assessed the impact of inhibiting actomyosin contractility on cell dedifferentiation.

Main Results:

• Observed sequential changes in colony morphology coupled with transcription program changes.
• Identified a bifurcation event in cell state transitions using morphology analysis.
• Demonstrated that inhibiting actomyosin contractility before bifurcation enhances dedifferentiation.
• Revealed that mechanical checkpoints influence cell state heterogeneity.

Conclusions:

• Actomyosin contractile forces are critical regulators of heterogeneous cell-fate decisions.
• Mechanical checkpoints exist that contribute to cell state heterogeneity.
• Cellular mechanics play a significant role in regulating cell state transitions and reprogramming.