title: Cadherin Diffusion in Supported Lipid Bilayers Exhibits Calcium-Dependent Dynamic Heterogeneity.
abstract: Ca2+ions are critical to cadherin ectodomain rigidity, which is required for the activation of adhesive functions. Therefore, changes in Ca2+concentration, both in vivo and in vitro, can affect cadherin conformation and function. We employed single-molecule tracking to measure the diffusion of cadherin ectodomains tethered to supported lipid bilayers at varying Ca2+concentrations. At a relatively high Ca2+concentration of 2 mM, cadherin molecules exhibited a fast diffusion coefficient that was identical to that of individual lipid molecules in the bilayer (Dfast≈ 3 μm2/s). At lower Ca2+concentrations, where cadherin molecules were less rigid, the ensemble-average cadherin diffusion coefficient was systematically smaller. Individual cadherin trajectories were temporally heterogeneous, exhibiting alternating periods of fast and slow diffusion; the periods of slow diffusion (Dslow≈ 0.1 μm2/s) were more prevalent at lower Ca2+concentration. These observations suggested that more flexible cadherin ectodomains at lower Ca2+concentration alternated between upright and lying-down conformations, where the latter interacted with more lipid molecules and experienced greater viscous drag.
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana-Champaign, Urbana, Illinois.
authors.forename: Nitesh
authors.initials: N
authors.lastname: Shashikanth
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana-Champaign, Urbana, Illinois.
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Leckband
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado. Electronic address: daniel.schwartz@colorado.edu.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Schwartz
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004058:Diffusion; D008051:Lipid Bilayers / Q000378:metabolism*
chemical_list: D015820:Cadherins; D008051:Lipid Bilayers; D002118:Calcium