title: Molecular Dynamics Simulation and Experimental Studies of Gold Nanoparticle Templated HDL-like Nanoparticles for Cholesterol Metabolism Therapeutics.
abstract: 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-pyridyldithio)propionate] 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 lecithin/cholesterol 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.
authors.affiliation: Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Cheng-Tsung
authors.identifier: http://orcid.org/0000-0002-1192-2815
authors.initials: CT
authors.lastname: Lai
authors.affiliation: Department of Urology, Northwestern University , Chicago, Illinois 60611, United States.|Simpson Querrey Institute for Bionanotechnology , 303 East Superior, Chicago, Illinois 60611, United States.|International Institute for Nanotechnology, 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Wangqiang
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Urology, Northwestern University , Chicago, Illinois 60611, United States.|Simpson Querrey Institute for Bionanotechnology , 303 East Superior, Chicago, Illinois 60611, United States.|International Institute for Nanotechnology, 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Rohun U
authors.initials: RU
authors.lastname: Palekar
authors.affiliation: Department of Urology, Northwestern University , Chicago, Illinois 60611, United States.|Simpson Querrey Institute for Bionanotechnology , 303 East Superior, Chicago, Illinois 60611, United States.|International Institute for Nanotechnology, 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: C Shad
authors.initials: CS
authors.lastname: Thaxton
authors.affiliation: Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: George C
authors.identifier: http://orcid.org/0000-0001-5837-4740
authors.initials: GC
authors.lastname: Schatz
mesh_terms: D002784:Cholesterol; D006046:Gold; D008075:Lipoproteins, HDL; D053768:Metal Nanoparticles; D056004:Molecular Dynamics Simulation
chemical_list: D008075:Lipoproteins, HDL; D006046:Gold; D002784:Cholesterol
keywords: HDL; LCAT; apolipoprotein A-I; cholesterol; cholesteryl ester; gold nanoparticle