Computational Modelling of Integrin Interactions Under an Electric Field

Abstract

Cell-material interactions involve the adsorption of proteins on material surfaces followed by biophysical interactions among adsorbed proteins and cell surface integrins. Molecular Dynamics (MD) simulations have been employed to gain atomistic insights into these complex phenomena with varying degrees of success. While MD studies on protein adsorption on material surfaces have gained significant traction, such studies on integrin-protein interactions within the extracellular space remains limited. This work aims to address this gap by providing mechanistic insights into the extracellular integrin-fibronectin interactions through the analysis of interaction energies and factors indicative of stability, such as root mean square deviation (RMSD) and centre-of-mass distance between interacting proteins. Moreover, higher affinity interactions between fibronectin and integrin will be reflected in the larger number of contacts established between them. Following this, kinetic modelling was conducted to investigate the effects of an electric field on focal adhesion complexes (FACs) using a coarse-grained ab-initio kinetic model. The results from this study reveal that the impact of the electric field on the concentration of mature adhesions is only observable at high field strengths. Further analysis indicates that the total force exerted by focal adhesions exhibits a more pronounced dependence on electric field strength. Additionally, a smaller number of vinculins are recruited into the FACs under high-field conditions. The mean actin retrograde velocity is also observed to increase with electric field strength, thereby impacting cell traction and downstream signalling pathways.