Albumin-Hyaluronan Interactions: Influence of Ionic Composition Probed by Molecular Dynamics.

Piotr Bełdowski,Przemysław Raczyński,Zbigniew Dendzik,Per M Claesson,Krzysztof Górny,Maciej Przybyłek,Florian Wieland,Alina Sionkowska,Andra Dedinaite

doi:10.3390/ijms222212360

Abstract

The lubrication mechanism in synovial fluid and joints is not yet fully understood. Nevertheless, intermolecular interactions between various neutral and ionic species including large macromolecular systems and simple inorganic ions are the key to understanding the excellent lubrication performance. An important tool for characterizing the intermolecular forces and their structural consequences is molecular dynamics. Albumin is one of the major components in synovial fluid. Its electrostatic properties, including the ability to form molecular complexes, are closely related to pH, solvation, and the presence of ions. In the context of synovial fluid, it is relevant to describe the possible interactions between albumin and hyaluronate, taking into account solution composition effects. In this study, the influence of Na+, Mg2+, and Ca2+ ions on human serum albumin–hyaluronan interactions were examined using molecular dynamics tools. It was established that the presence of divalent cations, and especially Ca2+, contributes mostly to the increase of the affinity between hyaluronan and albumin, which is associated with charge compensation in negatively charged hyaluronan and albumin. Furthermore, the most probable binding sites were structurally and energetically characterized. The indicated moieties exhibit a locally positive charge which enables hyaluronate binding (direct and water mediated).

Highlights

Degenerative joint diseases including the most common osteoarthritis causing synovial inflammation, osteophyte, and other articular cartilage damage processes is a global health problem that affects millions of people around the world [1,2]
The aim of this study is to evaluate the effect of Na+, Mg2+, Ca2+ cations on the affinity of hyaluronate (Figure 1) to human serum albumin using molecular dynamics methods
Since docking gives only preliminary information on the stability of the structure, the obtained complexes were enriched with water molecules and subjected to molecular dynamics simulation

Summary

Introduction

Degenerative joint diseases including the most common osteoarthritis causing synovial inflammation, osteophyte, and other articular cartilage damage processes is a global health problem that affects millions of people around the world [1,2]. It has been estimated that osteoarthritis affects over 25% of the adult population [1] From this point of view, a well working lubrication in an articular cartilage/synovial fluid system is important to maintain as this will ensure a high quality of life and low healthcare costs. The synovial fluid contains many diverse and important components, such as hyaluronan, phospholipids, and proteins such as γ-globulin, albumin, and lubricin that play major roles in the lubrication mechanism [4,5,6]. Albumin deserves special attention due to its binding and transporting properties of various compounds (fatty acids [7,8], bilirubin [9], steroids [10]) and ions, K+ , Na+ , and Mg2+ and Ca2+ [11,12,13,14,15,16,17,18,19]

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