MOLECULAR DYNAMICS SIMULATION AND EXPERIMENTAL STUDIES OF GOLD NANOPARTICLE TEMPLATED HDL-LIKE NANOPARTICLES FOR CHOLESTEROL (POSTPRINT)
NORTHWESTERN UNIV CHICAGO IL CHICAGO United States
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High-density lipoprotein HDL plays an important role in the transport and metabolism of cholesterol. Mimics of HDL are being explored as potentially powerful therapeutic agents for removing excess cholesterol from arterial plaques. Gold nanoparticles AuNPs functionalized with apolipoprotein A-I and with the lipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-3-2-pyridyldithiopropionate have been demonstrated to be robust acceptors of cellular cholesterol. However, detailed structural information about this functionalized HDL AuNP is still lacking. In this study, we have used X-ray photoelectron spectroscopy and lecithincholesterol acyltransferase activation experiments together with coarse-grained and all-atom molecular dynamics simulations to model the structure and cholesterol uptake properties of the HDL AuNP construct. By simulating different apolipoprotein-loaded AuNPs, we find that lipids are oriented differently in regions with and without apoA-I. We also show that in this functionalized HDL AuNP, the distribution of cholesteryl ester maintains a reverse concentration gradient that is similar to the gradient found in native HDL.
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- Atomic and Molecular Physics and Spectroscopy