Origins of synergy in multilipid lubrication.

Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE

Original Publication: Washington, DC : National Academy of Sciences

Lipid Bilayers*/chemistry ; Lipid Bilayers*/metabolism ; Lubrication* ; Molecular Dynamics Simulation*; Humans ; Synovial Fluid/metabolism ; Synovial Fluid/chemistry ; Lipids/chemistry

Lipid bilayers, ubiquitous in living systems, form lubricious boundary layers in aqueous media, with broad relevance for biolubrication, especially in mechanically stressed environments such as articular cartilage in joints, as well as for modifying material interfacial properties. Model studies have revealed efficient lubricity by single-component lipid bilayers; synovial joints, however (e.g. hips and knees), comprise over a hundred different lipids, raising the question of whether this is natural redundancy or whether it confers any lubrication benefits. Here, we examine lubrication by progressively more complex mixtures of lipids representative of those in joints, using a surface forces balance at physiologically relevant salt concentrations and pressures. We find that different combinations of such lipids differ very significantly in the robustness of the bilayers to hemifusion under physiological loads (when lubrication breaks down), indicating a clear lubrication synergy afforded by multiple lipid types in the bilayers. Insight into the origins of this synergy is provided by detailed molecular dynamics simulations of potential profiles for the formation of stalks, the essential precursors of hemifusion, between bilayers of the different lipid mixtures used in the experiments. These reveal how bilayer hemifusion-and thus lubrication breakdown-depends on the detailed lipid bilayer composition, through the corresponding separation into domains that are better able to resist stalk formation. Our results shed light on the role of lipid-type proliferation in biolubrication synergy, point to improved treatment modalities for common joint diseases such as osteoarthritis, and indicate how lipid-based interfacial modification in a materials context may be optimized.
Competing Interests: Competing interests statement:The authors declare no competing interest.

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743016 EC | European Research Council (ERC); 101069414 EC | European Research Council (ERC); N/A McCutchen Foundation (The McCutchen Foundation); 3-15716 Israel Ministry of Science and Technology; 1229/20 Israel Science Foundation (ISF); 3618/21 Israel Science Foundation - National Natural Science Foundation of China joint research program

Keywords: biolubrication; lipid bilayers; lipid mixtures; molecular dynamics; surface forces

0 (Lipid Bilayers)
0 (Lipids)

Date Created: 20241112 Date Completed: 20241112 Latest Revision: 20241127

20241202

PMC11588124

10.1073/pnas.2408223121

39531494