Molecular dynamics simulation and experimental studies of gold nanoparticle templated HDL-like nanoparticles for cholesterol metabolism therapeutics

Cheng Tsung Lai, Wangqiang Sun, Rohun U. Palekar, C. Shad Thaxton, George C Schatz

Research output: Contribution to journalArticle

3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1247-1254
Number of pages8
JournalACS Applied Materials and Interfaces
Issue number2
Publication statusPublished - Jan 1 2017



  • Apolipoprotein A-I
  • Cholesterol
  • Cholesteryl ester
  • Gold nanoparticle
  • HDL
  • LCAT

ASJC Scopus subject areas

  • Materials Science(all)

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