On the interaction of hyaluronic acid with synovial fluid lipid membranes

Smith, Paul; Ziolek, Robert M.; Gazzarrini, Elena; Owen, Dylan M.; Lorenz, Christian D.

doi:10.1039/c9cp01532a

Cited by 63 publications

(63 citation statements)

References 62 publications

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“…There was no significant difference between force profiles measured across the POPC dispersion and across HA–POPC mixture (0.5 mg/mL: 0.3 mM, Figure 5 b—red symbols) once HA was introduced. We may conclude the HA–POPC complex [ 34 , 56 ] was not trapped between the surface, but rather that it was squeezed out between POPC bilayers as the surfaces approached.…”

Section: Resultsmentioning

confidence: 99%

“…In the hydration lubrication paradigm surfaces interact via fluid but tenaciously attached hydration layers exposed by their boundary layers at the slip plane, resulting in low friction as surfaces slide past each other [ 12 , 58 ]. Previous studies [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 56 , 59 , 60 , 61 , 62 , 63 , 64 ] showed that HA interacts with PC lipids when they are dispersed in aqueous solution or when the phospholipids are incubated with pre-adsorbed HA on a surface, due to charge-dipole interactions between the negatively charged HA and the exposed zwitterionic phosphocholine headgroups. Thus one would expect that HA would adsorb at a phospholipid-bilayer/water interface.…”

Section: Discussionmentioning

confidence: 99%

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The Role of Hyaluronic Acid in Cartilage Boundary Lubrication

Lin

Liu

Kampf

et al. 2020

Cells

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Hydration lubrication has emerged as a new paradigm for lubrication in aqueous and biological media, accounting especially for the extremely low friction (friction coefficients down to 0.001) of articular cartilage lubrication in joints. Among the ensemble of molecules acting in the joint, phosphatidylcholine (PC) lipids have been proposed as the key molecules forming, in a complex with other molecules including hyaluronic acid (HA), a robust layer on the outer surface of the cartilage. HA, ubiquitous in synovial joints, is not in itself a good boundary lubricant, but binds the PC lipids at the cartilage surface; these, in turn, massively reduce the friction via hydration lubrication at their exposed, highly hydrated phosphocholine headgroups. An important unresolved issue in this scenario is why the free HA molecules in the synovial fluid do not suppress the lubricity by adsorbing simultaneously to the opposing lipid layers, i.e., forming an adhesive, dissipative bridge between them, as they slide past each other during joint articulation. To address this question, we directly examined the friction between two hydrogenated soy PC (HSPC) lipid layers (in the form of liposomes) immersed in HA solution or two palmitoyl–oleoyl PC (POPC) lipid layers across HA–POPC solution using a surface force balance (SFB). The results show, clearly and surprisingly, that HA addition does not affect the outstanding lubrication provided by the PC lipid layers. A possible mechanism indicated by our data that may account for this is that multiple lipid layers form on each cartilage surface, so that the slip plane may move from the midplane between the opposing surfaces, which is bridged by the HA, to an HA-free interface within a multilayer, where hydration lubrication is freely active. Another possibility suggested by our model experiments is that lipids in synovial fluid may complex with HA, thereby inhibiting the HA molecules from adhering to the lipids on the cartilage surfaces.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Role of Hyaluronic Acid in Cartilage Boundary Lubrication

Lin

Liu

Kampf

et al. 2020

Cells

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“…From the resulting set of 6114 residue pairs, we carried out further renements to identify a subset for which HBs were most likely to be present. A wide range of HB distance (2.2-4.0 A) and angle criteria (90-180 ) have been proposed [87][88][89] in the literature. Because consensus about HB distances and angles is not established, and the optimal HB distance or angle is strongly species dependent, we developed a quantummechanically derived approach to selecting distance and angle cutoffs.…”

Section: Curation Approachmentioning

confidence: 99%

When are two hydrogen bonds better than one? Accurate first-principles models explain the balance of hydrogen bond donors and acceptors found in proteins

Vennelakanti

Mehmood

et al. 2021

Chem. Sci.

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“…Block averaging was used to compute both the mean and standard deviation over the sampled trajectories. Dihedral angle and hydrogen bonding analyses were performed using the MDAnalysis package [89,90]. pKa analysis was performed using the DelPhiPKa webserver [91,92].…”

Section: Analysesmentioning

confidence: 99%

KEAP1 Cancer Mutants: A Large-Scale Molecular Dynamics Study of Protein Stability

Wilson

Chang

Karttunen

et al. 2021

IJMS

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We have performed 280 μs of unbiased molecular dynamics (MD) simulations to investigate the effects of 12 different cancer mutations on Kelch-like ECH-associated protein 1 (KEAP1) (G333C, G350S, G364C, G379D, R413L, R415G, A427V, G430C, R470C, R470H, R470S and G476R), one of the frequently mutated proteins in lung cancer. The aim was to provide structural insight into the effects of these mutants, including a new class of ANCHOR (additionally NRF2-complexed hypomorph) mutant variants. Our work provides additional insight into the structural dynamics of mutants that could not be analyzed experimentally, painting a more complete picture of their mutagenic effects. Notably, blade-wise analysis of the Kelch domain points to stability as a possible target of cancer in KEAP1. Interestingly, structural analysis of the R470C ANCHOR mutant, the most prevalent missense mutation in KEAP1, revealed no significant change in structural stability or NRF2 binding site dynamics, possibly indicating an covalent modification as this mutant’s mode of action.

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On the interaction of hyaluronic acid with synovial fluid lipid membranes

Abstract: All-atom molecular dynamics simulations have been used to investigate the adsorption of low molecular weight hyaluronic acid to lipid membranes.

Cited by 63 publications

References 62 publications

The Role of Hyaluronic Acid in Cartilage Boundary Lubrication

The Role of Hyaluronic Acid in Cartilage Boundary Lubrication

When are two hydrogen bonds better than one? Accurate first-principles models explain the balance of hydrogen bond donors and acceptors found in proteins

KEAP1 Cancer Mutants: A Large-Scale Molecular Dynamics Study of Protein Stability

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