Our latest manuscript entitled “On the interaction of hyaluronic acid with synovial fluid lipid membranes” features work by two PhD students in the lab (Paul Smith & Rob Ziolek) and an undergraduate student who worked with us last summer (Elena Gazzarrini). In this manuscript, we used all-atom molecular dynamics simulations to investigate how molecular weight of hyaluronic acid affects its interaction with lipid membranes. Specifically, we used a composition of lipid membranes that is consistent with that found in synovial fluid, which lubricates the articulate cartilage in synovial joints (e.g. knees, hips) during movement. These cartilage layers are really fascinating because as they slide past each other they exhibit very small amounts of friction (friction coefficients ~ 0.001) under physiologically high pressures (on the order of 100 atmospheres). This is a lubricating effect that no man-made surface can reproduce. As a result a lot of research has been conducted in better understanding what allows these synovial joints to enjoy such fantastic lubrication properties.
As a result, various different components of these biological lubricating systems have been identified including hyaluronic acid — a large molecular weight polysaccharide; lubricin — a proteoglycan; and phospholipids. A significant amount of experimental work has been conducted trying to identify which of these molecules or the combination of which hold the key to the lubrication properties so that they could potentially be reproduced synthetically. The current understanding is that all of these molecules must be present in the lubricating system in order to reproduce this kind of coefficient of friction at such high pressures. Seror et al. suggested a scenario where the “hyaluronic acid is anchored at the outer surface of articular cartilage by lubricin molecules, and complexes with joint phosphatidylcholines to provide the extreme lubrication of synovial joints via the hydration–lubrication mechanism.” Therefore in this manuscript, we wanted to take the first step into understanding the underlying molecular scale mechanisms which govern the interaction between hyaluronic acid and commonly found lipid bilayers in the synovial joints. In doing so, we found that water-mediated interactions play a very important role in stabilising the adsorbed structure of hyaluronic acid on the lipid bilayer interface. Additionally, after we compared the behaviour of hyaluronic acid with that of dextran — a polysaccharide which is not negatively charged like hyaluronic acid, we found that the electrostatic interactions between hyaluronic acid and the lipid bilayer also plays an important role in its interaction. Through these interactions, we have identified a potential mechanism by which hyaluronic acid can remain adsorbed to, and keep hydrated, lipid membranes when subjected to the pressures found in synovial joints.
Full reference: “On the interaction of hyaluronic acid with synovial fluid lipid membranes“, Paul Smith, Robert M. Ziolek, Elena Gazzarrini, Dylan M. Owen & Christian D. Lorenz, Physical Chemistry Chemical Physics (2019) 21, 9845-9857.