Molecular clutch drives cell response to surface viscosity

Area of Science:

• Biophysics
• Cell Biology
• Materials Science

Background:

• Cellular responses to the mechanical properties of the extracellular matrix are often explained by the molecular clutch model, involving actin, talin, integrin, and fibronectin.
• This model typically focuses on matrix elasticity, but cell interactions with viscous surfaces are less understood.

Purpose of the Study:

• To extend the molecular clutch model to explain cell interactions with purely viscous surfaces.
• To investigate how altering surface viscosity impacts cell behavior and downstream signaling pathways.

Main Methods:

• Utilized supported lipid bilayers with varying lipid diffusion coefficients to control surface viscosity and ligand mobility (RGD).
• Quantified cell size, cytoskeletal organization, focal adhesion formation, and focal adhesion kinase (FAK) phosphorylation.
• Measured actin retrograde flow, YAP protein localization, and myoblast differentiation.

Main Results:

• Cell size and cytoskeletal organization increased proportionally with viscosity.
• Less-mobile (higher viscosity) surfaces showed more focal adhesions and higher FAK phosphorylation.
• Actin retrograde flow was faster on more mobile (lower viscosity) surfaces.
• YAP localized to the nucleus more on less-mobile surfaces, and myoblast differentiation was enhanced on higher viscosity surfaces.

Conclusions:

• Surface viscosity, independent of matrix stiffness, significantly influences cell behavior and downstream signaling.
• Lower viscosity leads to low force loading rates, hindering mechanosensitive protein exposure, while higher viscosity increases force loading rates, activating these pathways.
• This understanding provides a new approach for engineering materials to control cellular responses.