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Title: Structure of Lung-Mimetic Multilamellar Bodies with Lipid Compositions Relevant in Pneumonia

Journal Article · · Langmuir

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. Furthermore, 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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC); US Department of the Navy, Office of Naval Research (ONR)
Grant/Contract Number:
AC02-06CH11357; N000141612886; N000141812087
OSTI ID:
1478088
Journal Information:
Langmuir, Vol. 34, Issue 25; ISSN 0743-7463
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 9 works
Citation information provided by
Web of Science

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