Computational modelling of fibronectin–integrin interactions under electric-field stimuli

Abstract

Cell–biomaterial interactions involve the adsorption of proteins on material surfaces, followed by biophysical interactions among adsorbed proteins and cell surface integrins. In a series of recent publications, it has been demonstrated that the cell fate processes can be guided by the electric field stimulations on a range of biomaterial substrates, in vitro. In efforts to understand the underlying biophysical process, molecular dynamics (MD) simulation studies indicated the role of electrical stimuli in fibronectin protein adsorption on biomaterial substrates. While molecular dynamics (MD) studies on protein adsorption on biomaterial surfaces have gained significant traction, such studies on integrin–protein interactions within the extracellular space remain relatively unexplored. Against this perspective, this work provides the mechanistic insights into the role of electric fields in fibronectin–integrin interactions and integrin clustering in the extracellular space. The present study involves the analysis of global descriptors, including interaction energy, root mean square deviation, radius of gyration, and center-of-mass distance, together with residue-level metrics such as residue–residue contact maps, hydrogen-bond and salt-bridge persistence, RGD-loop orientation, interfacial solvent-accessible surface area, and secondary-structure evolution among the interacting proteins, in a system comprising of 636 210 atoms. In summary, the outcomes of the present work enable a better understanding of the molecular mechanisms underlying exogenous electric-field-mediated cell–biomaterial interactions.