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Origins of synergy in multilipid lubrication
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2024-11-12 , DOI: 10.1073/pnas.2408223121
Yifeng Cao, Di Jin, Nir Kampf, Jacob Klein

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.

中文翻译:


多脂润滑协同作用的起源



脂质双层在生命系统中无处不在,在水性介质中形成润滑边界层,与生物润滑具有广泛的相关性,尤其是在机械应力环境中,例如关节中的关节软骨,以及改变材料界面特性。模型研究表明,单组分脂质双层具有有效的润滑性;然而,滑膜关节(例如髋关节和膝关节)包含一百多种不同的脂质,这引发了这样一个问题:这是自然冗余还是它是否赋予了任何润滑益处。在这里,我们使用生理相关盐浓度和压力下的表面力平衡,通过逐渐更复杂的脂质混合物来检查润滑。我们发现,在生理负荷下(当润滑失效时),这种脂质的不同组合在双层对半融合的稳健性方面存在非常显着的差异,这表明双层中的多种脂质类型具有明显的润滑协同作用。通过对实验中使用的不同脂质混合物的双层之间形成茎秆(半融合的重要前体)的潜在轮廓的详细分子动力学模拟,可以深入了解这种协同作用的起源。这些揭示了双层半融合(以及润滑分解)如何取决于详细的脂质双层组成,通过相应的分离成能够更好地抵抗茎形成的结构域。我们的结果阐明了脂质类型增殖在生物润滑协同作用中的作用,指出了骨关节炎等常见关节疾病的改进治疗方式,并表明了如何在材料环境中优化基于脂质的界面修饰。
更新日期:2024-11-12
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