Adsorption of Fibronectin Fragment on Surfaces Using Fully Atomistic Molecular Dynamics Simulations.

Evangelos Liamas,Owen Thomas,Paul Mulheran,Zhenyu Zhang,Richard Black,Karina Kubiak-Ossowska

doi:10.3390/ijms19113321

Evangelos Liamas, Owen Thomas + Show 4 more

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https://doi.org/10.3390/ijms19113321

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Abstract

The effect of surface chemistry on the adsorption characteristics of a fibronectin fragment (FNIII8–10) was investigated using fully atomistic molecular dynamics simulations. Model surfaces were constructed to replicate self-assembled monolayers terminated with methyl, hydroxyl, amine, and carboxyl moieties. It was found that adsorption of FNIII8–10 on charged surfaces is rapid, specific, and driven by electrostatic interactions, and that the anchoring residues are either polar uncharged or of opposing charge to that of the targeted surfaces. On charged surfaces the presence of a strongly bound layer of water molecules and ions hinders FNIII8–10 adsorption. In contrast, adsorption kinetics on uncharged surfaces are slow and non-specific, as they are driven by van der Waals interactions, and the anchoring residues are polar uncharged. Due to existence of a positively charged area around its cell-binding region, FNIII8–10 is available for subsequent cell binding when adsorbed on a positively charged surface, but not when adsorbed on a negatively charged surface. On uncharged surfaces, the availability of the fibronectin fragment’s cell-binding region is not clearly distinguished because adsorption is much less specific.

Highlights

Biomaterials are generally defined as materials that interact with living matter and can be used to construct tissue and organs in order to replace or augment the function of their predecessors [1]
Simulation results confirm that electrostatics are the main driving forces for the adsorption of fibronectin fragment on the positively charged systems while in the case of negatively charged surface the picture is slightly more complicated
All simulations were performed with the NAMD 2.6 package, using the Charmm27 force field, while the images were analysed with the VMD software [41,42]

Summary

Introduction

Biomaterials are generally defined as materials that interact with living matter and can be used to construct tissue and organs in order to replace or augment the function of their predecessors [1]. It is a main cell receptor that influences processes such as cell adhesion and differentiation, while it is involved in applications such as inflammation and wound repair [7]. It has a molecular weight of approximately 440 kDa and consists of two similar chains held together by a couple of disulphide bonds at the C-terminus. Fibronectin contains a cell-recognition sequence that allows it to bind with integrins on the surface of cells. It is composed of the cell binding and the synergy domains which respectively contain the amino acid sequences Arg–Gly–Asp (RGD) and Pro–His–Ser–Arg–Asn (PHSRN). In order for the cell to bind fibronectin, it is crucial that the cell-binding domain remains exposed to solvent after adsorption, because mismatched conformation or denaturation of the protein will inhibit binding to cells [9]

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