Cadherin Extracellular Domain Clustering in the Absence of Trans-Interactions

Connor J. Thompson, Vinh H. Vu, Deborah E. Leckband, Daniel K. Schwartz

Research output: Contribution to journalArticlepeer-review

Abstract

While both cis and trans (adhesive)-interactions cooperate in the assembly of intercellular adhesions, computational simulations have predicted that two-dimensional confinement may promote cis-oligomerization, in the absence of trans-interactions. Here, single-molecule tracking of cadherin extracellular domains on supported lipid bilayers revealed the density-dependent formation of oligomers and cis-clusters in the absence of trans-interactions. Lateral oligomers were virtually eliminated by mutating a putative cis (lateral) binding interface. At low cadherin surface coverage, wild-type and mutant cadherin diffused rapidly, consistent with the motion of a lipid molecule within a cadherin-free supported bilayer and with cadherins diffusing as monomers. Although the diffusion of mutant cadherin did not change appreciably with increasing surface coverage, the average short-time diffusion coefficient of wild-type cadherin slowed significantly above a fractional surface coverage of ∼0.01 (∼1100 molecules/μm2). A detailed analysis of molecular trajectories suggested the presence of a broad size distribution of cis-cadherin oligomers. These findings verify predictions that two-dimensional confinement promotes cis-oligomerization, in the absence of trans-interactions.

Original languageEnglish (US)
Pages (from-to)4528-4534
Number of pages7
JournalJournal of Physical Chemistry Letters
Volume10
Issue number16
DOIs
StatePublished - Aug 15 2019

ASJC Scopus subject areas

  • Materials Science(all)
  • Physical and Theoretical Chemistry

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