Correlations in cadherin-mediated membrane adhesion dynamics: Molecular concentration switch and diffusion dial

Area of Science:

• Biophysics
• Materials Science
• Cell Biology

Background:

• Cell adhesion is crucial for physiological processes but its dynamics, especially with weak bonds, remain poorly understood.
• The interplay between bond kinetics and large-scale adhesion dynamics in lipid membranes requires further investigation.

Purpose of the Study:

• To investigate the influence of binder concentration and diffusion on membrane adhesion dynamics.
• To elucidate the multiscale mechanisms coupling cadherin bond kinetics with vesicle-membrane adhesion.

Main Methods:

• Utilized Reflection Interference Contrast Microscopy (RICM) to observe adhesion dynamics between cadherin-decorated giant unilamellar vesicles (GUVs) and supported lipid bilayers (SLBs).
• Systematically varied cadherin concentration and mobility on both GUVs and SLBs.
• Developed multiscale Monte Carlo simulations with an adaptive Euler method to model GUV spreading dynamics.

Main Results:

• Adhesion dynamics and equilibrium are strongly dependent on cadherin concentration, with higher concentrations promoting faster and stronger adhesion.
• Cadherin mobility on the supported lipid bilayer significantly enhances and accelerates adhesion compared to immobile cadherins.
• Simulations demonstrated that membrane-mediated trans-interactions recruit receptors into the adhesion zone, driven by chemical potential equilibration in large cadherin agglomerates.

Conclusions:

• Binder concentration is the dominant factor in membrane adhesion dynamics, overriding diffusion effects.
• Cooperative effects arising from cadherin mobility and trans-binding enhance adhesion, providing a comprehensive model for vesicle-membrane interactions.
• The study reveals critical insights into the coupling of force-sensitive cadherin kinetics and membrane mechanics during adhesion processes.