Cadherin Extracellular Domain Clustering in the Absence of Trans-Interactions

Area of Science:

• Cell biology
• Biophysics
• Molecular dynamics

Background:

• Intercellular adhesions rely on both cis and trans cadherin interactions.
• Computational models suggest 2D confinement may drive cis-oligomerization without trans-interactions.

Purpose of the Study:

• To experimentally investigate cadherin cis-oligomerization under 2D confinement.
• To validate predictions of confinement-induced cis-oligomerization in the absence of trans-interactions.

Main Methods:

• Single-molecule tracking of cadherin extracellular domains on supported lipid bilayers.
• Utilized wild-type and mutant cadherins with a mutated cis binding interface.
• Analyzed molecular trajectories and diffusion coefficients at varying surface coverages.

Main Results:

• Observed density-dependent formation of cadherin oligomers and cis-clusters on lipid bilayers.
• Mutating the cis binding interface significantly reduced lateral oligomer formation.
• Wild-type cadherin diffusion slowed with increasing surface coverage, indicating oligomerization.

Conclusions:

• Confirmed that 2D confinement promotes cis-cadherin oligomerization independently of trans-interactions.
• Demonstrated the formation of a broad size distribution of cis-cadherin oligomers.
• Provided experimental evidence supporting computational predictions of confinement effects on protein interactions.