Molecular Mechanisms of Cell Adhesion

NCAM forms a complex between its terminal domains Ig1 and Ig2. When NCAM of cell A and 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. Here we investigate 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 equilibrate the complex in solvent and show that its actual end-to-end length is markedly larger than in the crystal structure. We then show that the Ig12/Ig12 complex can behave as a molecular spring of spring constant ∼0.03 N/m in response to forces of tens of pico-Newton. Such tertiary structure elasticity can be expected to be pervasive considering the large number of multi-modular CAMs. Finally, we rupture the complex using higher forces to identify E16, F19, K98, and L175 as key residues stabilizing the complex.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Maruthamuthu, Venkat

Contributors dc:contributor

• Leckband, Deborah E.

• Chemistry, Biochemistry

Language dc:language

eng

Identifier

(MiAaPQ)AAI3363031

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/82423