Reinforcement versus fluidization in cytoskeletal mechanoresponsiveness

Area of Science:

• Cell biology
• Biophysics
• Mechanobiology

Background:

• Eukaryotic cells generate traction forces and experience mechanical stretches in various tissues.
• Cellular responses to stretch, including stiffening or softening, are inconsistently reported.
• The underlying mechanisms and prevailing response to mechanical stretch remain unclear.

Purpose of the Study:

• To investigate the cellular response to mechanical stretch under physiological conditions.
• To differentiate between reinforcement and fluidization responses of the cytoskeleton.
• To elucidate the mechanisms driving cytoskeletal mechanical responses.

Main Methods:

• Utilized novel nanotechnology to apply controlled mechanical forces to cells.
• Simulated physiological loading conditions relevant to tissues like the heart, lungs, and gut.
• Analyzed cytoskeletal behavior and force generation in response to localized and homogeneous cell stretching.

Main Results:

• Under physiological loading, localized reinforcement responses do not scale effectively.
• Cytoskeletal fluidization predominates over reinforcement during homogeneous cell stretch.
• Fluidization is identified as a direct physical consequence of mechanical force on a soft, fragile cytoskeletal lattice.
• Reinforcement is mediated by mechanosensing and signaling pathways.

Conclusions:

• Cytoskeletal fluidization is a novel, direct physical response to mechanical force, distinct from signaling-dependent reinforcement.
• The observed softness and fragility of the cytoskeleton may reflect evolutionary adaptations to soft extracellular environments.
• Understanding these mechanical responses is crucial for comprehending cell behavior in physiological and pathological contexts.