Cell mechanosensing is regulated by substrate strain energy rather than stiffness

Area of Science:

• Cell Biology
• Biophysics
• Materials Science

Background:

• Cellular mechanosensing, the perception of mechanical cues from the extracellular matrix, is crucial for cell behavior.
• Existing models often focus on substrate stiffness, but the role of deformation energy remains debated.

Purpose of the Study:

• To investigate whether cells sense substrate stiffness or the energy required to deform the material.
• To evaluate the effect of prestrain on cell cytoskeleton mechanics.

Main Methods:

• Studied cytoskeleton mechanics of BALB/3T3 and MC3T3 cells on linearly elastic substrates with varying prestrain levels.
• Compared cell mechanics on prestrained substrates to those on unstrained substrates and substrates stretched post-seeding.

Main Results:

• Cells exhibited stiffer cytoskeletons on prestrained substrates compared to unstrained ones.
• Cell mechanics on prestrained substrates were similar to those after simultaneous stretching of substrate and cells.
• The clutch model, based solely on stiffness, could not explain the results.

Conclusions:

• Cell mechanosensing is influenced by both substrate stiffness and the associated deformation energy.
• A modified clutch model incorporating strain energy accurately interprets experimental findings.
• This highlights a more complex mechanism in how cells perceive their mechanical environment.