Molecular basis of conformational changes and mechanics of integrins

Abstract

Integrin, as a mechanotransducer, establishes the mechanical reciprocity between the extracellular matrix (ECM) and cells at integrin-mediated adhesion sites. This study used steered molecular dynamics (SMD) simulations to investigate the mechanical responses of integrin α v β 3 with and without 10th type III fibronectin (FnIII 10 ) binding for tensile, bending and torsional loading conditions. The ligand-binding integrin confirmed the integrin activation during equilibration and altered the integrin dynamics by changing the interface interaction between β-tail, hybrid and epidermal growth factor domains during initial tensile loading. The tensile deformation in integrin molecules indicated that fibronectin ligand binding modulates its mechanical responses in the folded and unfolded conformation states. The bending deformation responses of extended integrin models reveal the change in behaviour of integrin molecules in the presence of Mn 2+ ion and ligand based on the application of force in the folding and unfolding directions of integrin. Furthermore, these SMD simulation results were used to predict the mechanical properties of integrin underlying the mechanism of integrin-based adhesion. The evaluation of integrin mechanics provides new insights into understanding the mechanotransmission (force transmission) between cells and ECM and contributes to developing an accurate model for integrin-mediated adhesion. This article is part of a discussion meeting issue ‘Supercomputing simulations of advanced materials’.

Supercomputing modelling of advanced materials: preface

“…Modelling has for many years played an important role in understanding the processes of crystallization, which are the focus of two contributions [9-10]: Deymier et al describe the modelling of the effect of stress on the recrystallization and dissolution of apatite-key processes in bone mineralization-while Rogal et al describe how liquid structure and dynamics can provide information on crystal nucleation mechanisms. The breadth of the field is illustrated by the articles of Ahmad et al [11] who describe the modelling of the adsorption of organic molecules on the surface of alumina which they show is relevant to the understanding of organic matter in soils, and by Gaikwad et al [12] who employ steered molecular dynamics to model integrins-transmembrane adhesion proteins-with their work providing a model for integrinmediated adhesion. Several contributions report significant technical advances.…”

“…describe how liquid structure and dynamics can provide information on crystal nucleation mechanisms. The breadth of the field is illustrated by the articles of Ahmad et al [ 11 ] who describe the modelling of the adsorption of organic molecules on the surface of alumina which they show is relevant to the understanding of organic matter in soils, and by Gaikwad et al [ 12 ] who employ steered molecular dynamics to model integrins—transmembrane adhesion proteins—with their work providing a model for integrin-mediated adhesion. Several contributions report significant technical advances.…”