Single molecule tracking of cadherin extracellular domains on supported lipid bilayers revealed the density-dependent formation of oligomers and clusters due to cis-interactions, which were virtually eliminated by mutating a putative cis (lateral) binding interface. At low cadherin surface coverage, wild-type (WT) and mutant cadherin diffused rapidly, consistent with the motion of a lipid molecule within the supported bilayer. Although the diffusion of mutant cadherin did not change appreciably with surface coverage, the average short-time diffusion coefficient of WT cadherin slowed significantly above a fractional surface coverage of ~0.01, and a detailed analysis of molecular trajectories suggested the presence of a broad distribution of cadherin cluster sizes. Since cis-interactions have not been successfully detected between cadherin in homogeneous solution, these findings suggest that cis-interactions are strongly influenced by two-dimensional confinement.

Cadherin cluster formation in two dimensional confinement

2019 Fall National Meeting

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