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

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

Research output: Contribution to journalArticle

Abstract

Ca 2+ ions are critical to cadherin ectodomain rigidity, which is required for the activation of adhesive functions. Therefore, changes in Ca 2+ 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 Ca 2+ concentrations. At a relatively high Ca 2+ 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 μm 2 /s). At lower Ca 2+ 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 μm 2 /s) were more prevalent at lower Ca 2+ concentration. These observations suggested that more flexible cadherin ectodomains at lower Ca 2+ concentration alternated between upright and lying-down conformations, where the latter interacted with more lipid molecules and experienced greater viscous drag.

Original languageEnglish (US)
Pages (from-to)2658-2665
Number of pages8
JournalBiophysical journal
Volume111
Issue number12
DOIs
StatePublished - Dec 20 2016

Fingerprint

Lipid Bilayers
Cadherins
Calcium
Lipids
Adhesives
Ions

ASJC Scopus subject areas

  • Biophysics

Cite this

Cadherin Diffusion in Supported Lipid Bilayers Exhibits Calcium-Dependent Dynamic Heterogeneity. / Cai, Yu; Shashikanth, Nitesh; Leckband, Deborah E.; Schwartz, Daniel K.

In: Biophysical journal, Vol. 111, No. 12, 20.12.2016, p. 2658-2665.

Research output: Contribution to journalArticle

Cai, Yu ; Shashikanth, Nitesh ; Leckband, Deborah E. ; Schwartz, Daniel K. / Cadherin Diffusion in Supported Lipid Bilayers Exhibits Calcium-Dependent Dynamic Heterogeneity. In: Biophysical journal. 2016 ; Vol. 111, No. 12. pp. 2658-2665.
@article{43989495cb0448d6af766450179b1660,
title = "Cadherin Diffusion in Supported Lipid Bilayers Exhibits Calcium-Dependent Dynamic Heterogeneity",
abstract = "Ca 2+ ions are critical to cadherin ectodomain rigidity, which is required for the activation of adhesive functions. Therefore, changes in Ca 2+ 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 Ca 2+ concentrations. At a relatively high Ca 2+ 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 μm 2 /s). At lower Ca 2+ 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 μm 2 /s) were more prevalent at lower Ca 2+ concentration. These observations suggested that more flexible cadherin ectodomains at lower Ca 2+ concentration alternated between upright and lying-down conformations, where the latter interacted with more lipid molecules and experienced greater viscous drag.",
author = "Yu Cai and Nitesh Shashikanth and Leckband, {Deborah E.} and Schwartz, {Daniel K.}",
year = "2016",
month = "12",
day = "20",
doi = "10.1016/j.bpj.2016.10.037",
language = "English (US)",
volume = "111",
pages = "2658--2665",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "12",

}

TY - JOUR

T1 - Cadherin Diffusion in Supported Lipid Bilayers Exhibits Calcium-Dependent Dynamic Heterogeneity

AU - Cai, Yu

AU - Shashikanth, Nitesh

AU - Leckband, Deborah E.

AU - Schwartz, Daniel K.

PY - 2016/12/20

Y1 - 2016/12/20

N2 - Ca 2+ ions are critical to cadherin ectodomain rigidity, which is required for the activation of adhesive functions. Therefore, changes in Ca 2+ 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 Ca 2+ concentrations. At a relatively high Ca 2+ 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 μm 2 /s). At lower Ca 2+ 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 μm 2 /s) were more prevalent at lower Ca 2+ concentration. These observations suggested that more flexible cadherin ectodomains at lower Ca 2+ concentration alternated between upright and lying-down conformations, where the latter interacted with more lipid molecules and experienced greater viscous drag.

AB - Ca 2+ ions are critical to cadherin ectodomain rigidity, which is required for the activation of adhesive functions. Therefore, changes in Ca 2+ 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 Ca 2+ concentrations. At a relatively high Ca 2+ 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 μm 2 /s). At lower Ca 2+ 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 μm 2 /s) were more prevalent at lower Ca 2+ concentration. These observations suggested that more flexible cadherin ectodomains at lower Ca 2+ concentration alternated between upright and lying-down conformations, where the latter interacted with more lipid molecules and experienced greater viscous drag.

UR - http://www.scopus.com/inward/record.url?scp=85006710913&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006710913&partnerID=8YFLogxK

U2 - 10.1016/j.bpj.2016.10.037

DO - 10.1016/j.bpj.2016.10.037

M3 - Article

C2 - 28002742

AN - SCOPUS:85006710913

VL - 111

SP - 2658

EP - 2665

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 12

ER -