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 journalArticle

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

Fingerprint

Cadherins
Oligomers
Oligomerization
oligomers
Molecules
lipids
molecular trajectories
Lipid bilayers
interactions
molecules
Lipids
Adhesives
Adhesion
Monomers
Trajectories
adhesives
adhesion
diffusion coefficient
monomers
assembly

ASJC Scopus subject areas

  • Materials Science(all)
  • Physical and Theoretical Chemistry

Cite this

Cadherin Extracellular Domain Clustering in the Absence of Trans-Interactions. / Thompson, Connor J.; Vu, Vinh H.; Leckband, Deborah E; Schwartz, Daniel K.

In: Journal of Physical Chemistry Letters, Vol. 10, No. 16, 15.08.2019, p. 4528-4534.

Research output: Contribution to journalArticle

Thompson, Connor J. ; Vu, Vinh H. ; Leckband, Deborah E ; Schwartz, Daniel K. / Cadherin Extracellular Domain Clustering in the Absence of Trans-Interactions. In: Journal of Physical Chemistry Letters. 2019 ; Vol. 10, No. 16. pp. 4528-4534.
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