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ARTICLE

Effects of Altered Restraints in β1 Integrin on the Force-Regulated Interaction between the Glycosylated I-Like Domain of β1 Integrin and Fibronectin III_9-10: A Steered Molecular Dynamic Study

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* Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL 35294
† To whom correspondence should be addressed: Department of Biomedical Engineering, The University of Alabama at Birmingham, 803 Shelby Interdisciplinary Biomedical Research Building, 1825 University Boulevard, Birmingham, AL 35294. Phone: (205) 996-6939, Fax: (205) 975-4919, Email: yhsong@uab.edu, Web: http://www.eng.uab.edu/yhsong

Molecular & Cellular Biomechanics 2011, 8(3), 233-252. https://doi.org/10.3970/mcb.2011.008.233

Abstract

Cytoskeletal restraints affect force-regulated integrin function in cell adhesion. However, the structural and molecular basis underlying the effect of cytoskeletal restraints on b1 integrin binding to fibronectin is still largely unknown. In this study, we used steered molecular dynamics simulations to investigate the changes in glycosylated b1 integrin-fibronectin binding and in conformation and structure of the glycosylated b1 I-like domain-FN-III9 - 10 complex caused by altered restraints applied to b1 I-like domain. The results revealed that imposition of the increased constraints on b1 integrin increased resistance to force-induced dissociation of the b1 I-like domain-fibronectin complex. Specifically, the increased constraints enhanced resistance to relative conformational changes in the RGD-synergy site in fibronectin, increased the conformational stability of fibronectin, and prevented losses in hydrogen bond occupancy of each b-strand pair in FN-III10 resulting from external force. The increased constraints also resulted in an increase in correlated motion between residues in the b1 I-like domain, which may directly affect the interaction of b1 integrin with fibronectin. Results from this study provide molecular and structural insights into the effects of altered restraints in b1 integrin on the interaction between glycosylated b1 Integrin and fibronectin and its induced cell adhesion.

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