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- W2805211023 abstract "The hierarchical assembly of lipids, as modulated by composition and environment, plays a significant role in the function of biological membranes and a myriad of diseases. Elevated concentrations of calcium ions and cardiolipin (CL), an anionic tetra-alkyl lipid found in mitochondria and some bacterial cell membranes, have been implicated in pneumonia recently. However, their impact on the physicochemical properties of lipid assemblies in lungs and how it impairs alveoli function is still unknown. We use small- and wide-angle X-ray scattering (S/WAXS) and solid-state nuclear magnetic resonance (ssNMR) to probe the structure and dynamics of lung-mimetic multilamellar bodies (MLBs) in the presence of Ca2+ and CL. We conjecture that CL overexpressed in the hypophase of alveoli strongly affects the structure of lung-lipid bilayers and their stacking in the MLBs. Specifically, S/WAXS data revealed that CL induces significant shrinkage of the water-layer separating the concentric bilayers in multilamellar aggregates. ssNMR measurements indicate that this interbilayer tightening is due to undulation repulsion damping as CL renders the glycerol backbone of the membranes significantly more static. In addition to MLB dehydration, CL promotes intrabilayer phase separation into saturated-rich and unsaturated-rich lipid domains that couple across multiple layers. Expectedly, addition of Ca2+ screens the electrostatic repulsion between negatively charged lung membranes. However, when CL is present, addition of Ca2+ results in an apparent interbilayer expansion likely due to local structural defects. Combining S/WAXS and ssNMR on systems with compositions pertinent to healthy and unhealthy lung membranes, we propose how alteration of the physiochemical properties of MLBs can critically impact the breathing cycle." @default.
- W2805211023 created "2018-06-13" @default.
- W2805211023 creator A5016355209 @default.
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- W2805211023 creator A5088834377 @default.
- W2805211023 date "2018-05-30" @default.
- W2805211023 modified "2023-09-27" @default.
- W2805211023 title "Structure of Lung-Mimetic Multilamellar Bodies with Lipid Compositions Relevant in Pneumonia" @default.
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- W2805211023 doi "https://doi.org/10.1021/acs.langmuir.8b01359" @default.
- W2805211023 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29847137" @default.
- W2805211023 hasPublicationYear "2018" @default.
- W2805211023 type Work @default.