Cadherin Diffusion in Supported Lipid Bilayers Exhibits Calcium-Dependent Dynamic Heterogeneity

Journal Article · Thu Dec 01 00:00:00 EST 2016 · Biophysical Journal

DOI:https://doi.org/10.1016/j.bpj.2016.10.037· OSTI ID:1414302

Cai, Yu; Shashikanth, Nitesh; Leckband, Deborah E.; Schwartz, Daniel K.

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 ($$D$$_fast ≈ 3 $$μ$$m²/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 ($$D$$_slow ≈ 0.1 $$μ$$m²/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.

• Research Organization: Univ. of Colorado, Boulder, CO (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
• Grant/Contract Number: SC0001854; 5RO1-GM097443
• OSTI ID: 1414302
• Alternate ID(s): OSTI ID: 1396861; OSTI ID: 1533579
• Journal Information: Biophysical Journal, Journal Name: Biophysical Journal Vol. 111 Journal Issue: 12; ISSN 0006-3495
• Publisher: Elsevier
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biophysics