Elasticity and rupture of a multi-domain neural cell adhesion molecule complex

Venkat Maruthamuthu, Klaus Schulten, Deborah Leckband

Research output: Contribution to journalArticle

Abstract

The neural cell adhesion molecule (NCAM) plays an important role in nervous system development. NCAM forms a complex between its terminal domains Ig1 and Ig2. When NCAM of cell A and of cell B connect to each other through complexes Ig12(A)/Ig12(B), the relative mobility of cells A and B and membrane tension exerts a force on the Ig12(A)/Ig12(B) complex. In this study, we investigated the response of the complex to force, using steered molecular dynamics. Starting from the structure of the complex from the Ig1-Ig2-Ig3 fragment, we first demonstrated that the complex, which differs in dimensions from a previous structure from the Ig1-Ig2 fragment in the crystal environment, assumes the same extension when equilibrated in solvent. We then showed that, when the Ig12(A)/Ig12(B) complex is pulled apart with forces 30-70 pN, it exhibits elastic behavior (with a spring constant of ∼0.03 N/m) because of the relative reorientation of domains Ig1 and Ig2. At higher forces, the complex ruptures; i.e., Ig12(A) and Ig12(B) separate. The interfacial interactions between Ig12(A) and Ig12(B), monitored throughout elastic extension and rupture, identify E16, F19, K98, and L175 as key side chains stabilizing the complex.

Original languageEnglish (US)
Pages (from-to)3005-3014
Number of pages10
JournalBiophysical journal
Volume96
Issue number8
DOIs
StatePublished - Jan 1 2009

Fingerprint

Neural Cell Adhesion Molecules
Elasticity
Rupture
Molecular Dynamics Simulation
Nervous System
Membranes

ASJC Scopus subject areas

  • Biophysics

Cite this

Elasticity and rupture of a multi-domain neural cell adhesion molecule complex. / Maruthamuthu, Venkat; Schulten, Klaus; Leckband, Deborah.

In: Biophysical journal, Vol. 96, No. 8, 01.01.2009, p. 3005-3014.

Research output: Contribution to journalArticle

Maruthamuthu, Venkat ; Schulten, Klaus ; Leckband, Deborah. / Elasticity and rupture of a multi-domain neural cell adhesion molecule complex. In: Biophysical journal. 2009 ; Vol. 96, No. 8. pp. 3005-3014.
@article{7e1e321b813646669d000d90945ffe15,
title = "Elasticity and rupture of a multi-domain neural cell adhesion molecule complex",
abstract = "The neural cell adhesion molecule (NCAM) plays an important role in nervous system development. NCAM forms a complex between its terminal domains Ig1 and Ig2. When NCAM of cell A and of cell B connect to each other through complexes Ig12(A)/Ig12(B), the relative mobility of cells A and B and membrane tension exerts a force on the Ig12(A)/Ig12(B) complex. In this study, we investigated the response of the complex to force, using steered molecular dynamics. Starting from the structure of the complex from the Ig1-Ig2-Ig3 fragment, we first demonstrated that the complex, which differs in dimensions from a previous structure from the Ig1-Ig2 fragment in the crystal environment, assumes the same extension when equilibrated in solvent. We then showed that, when the Ig12(A)/Ig12(B) complex is pulled apart with forces 30-70 pN, it exhibits elastic behavior (with a spring constant of ∼0.03 N/m) because of the relative reorientation of domains Ig1 and Ig2. At higher forces, the complex ruptures; i.e., Ig12(A) and Ig12(B) separate. The interfacial interactions between Ig12(A) and Ig12(B), monitored throughout elastic extension and rupture, identify E16, F19, K98, and L175 as key side chains stabilizing the complex.",
author = "Venkat Maruthamuthu and Klaus Schulten and Deborah Leckband",
year = "2009",
month = "1",
day = "1",
doi = "10.1016/j.bpj.2008.12.3936",
language = "English (US)",
volume = "96",
pages = "3005--3014",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "8",

}

TY - JOUR

T1 - Elasticity and rupture of a multi-domain neural cell adhesion molecule complex

AU - Maruthamuthu, Venkat

AU - Schulten, Klaus

AU - Leckband, Deborah

PY - 2009/1/1

Y1 - 2009/1/1

N2 - The neural cell adhesion molecule (NCAM) plays an important role in nervous system development. NCAM forms a complex between its terminal domains Ig1 and Ig2. When NCAM of cell A and of cell B connect to each other through complexes Ig12(A)/Ig12(B), the relative mobility of cells A and B and membrane tension exerts a force on the Ig12(A)/Ig12(B) complex. In this study, we investigated the response of the complex to force, using steered molecular dynamics. Starting from the structure of the complex from the Ig1-Ig2-Ig3 fragment, we first demonstrated that the complex, which differs in dimensions from a previous structure from the Ig1-Ig2 fragment in the crystal environment, assumes the same extension when equilibrated in solvent. We then showed that, when the Ig12(A)/Ig12(B) complex is pulled apart with forces 30-70 pN, it exhibits elastic behavior (with a spring constant of ∼0.03 N/m) because of the relative reorientation of domains Ig1 and Ig2. At higher forces, the complex ruptures; i.e., Ig12(A) and Ig12(B) separate. The interfacial interactions between Ig12(A) and Ig12(B), monitored throughout elastic extension and rupture, identify E16, F19, K98, and L175 as key side chains stabilizing the complex.

AB - The neural cell adhesion molecule (NCAM) plays an important role in nervous system development. NCAM forms a complex between its terminal domains Ig1 and Ig2. When NCAM of cell A and of cell B connect to each other through complexes Ig12(A)/Ig12(B), the relative mobility of cells A and B and membrane tension exerts a force on the Ig12(A)/Ig12(B) complex. In this study, we investigated the response of the complex to force, using steered molecular dynamics. Starting from the structure of the complex from the Ig1-Ig2-Ig3 fragment, we first demonstrated that the complex, which differs in dimensions from a previous structure from the Ig1-Ig2 fragment in the crystal environment, assumes the same extension when equilibrated in solvent. We then showed that, when the Ig12(A)/Ig12(B) complex is pulled apart with forces 30-70 pN, it exhibits elastic behavior (with a spring constant of ∼0.03 N/m) because of the relative reorientation of domains Ig1 and Ig2. At higher forces, the complex ruptures; i.e., Ig12(A) and Ig12(B) separate. The interfacial interactions between Ig12(A) and Ig12(B), monitored throughout elastic extension and rupture, identify E16, F19, K98, and L175 as key side chains stabilizing the complex.

UR - http://www.scopus.com/inward/record.url?scp=67649394763&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649394763&partnerID=8YFLogxK

U2 - 10.1016/j.bpj.2008.12.3936

DO - 10.1016/j.bpj.2008.12.3936

M3 - Article

C2 - 19383447

AN - SCOPUS:67649394763

VL - 96

SP - 3005

EP - 3014

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 8

ER -