Lipid composition dictates serum stability of reconstituted high-density lipoproteins: Implications for: In vivo applications

Sean F. Gilmore, Timothy S. Carpenter, Helgi I. Ingólfsson, Sandra K.G. Peters, Paul Henderson, Craig D. Blanchette, Nicholas O Fischer

Research output: Contribution to journalArticle

Abstract

Nanolipoprotein particles (NLPs) are reconstituted high-density lipoproteins, consisting of a phospholipid bilayer stabilized by an apolipoprotein scaffold protein. This class of nanoparticle has been a vital tool in the study of membrane proteins, and in recent years has been increasingly used for in vivo applications. Previous work demonstrated that the composition of the lipid bilayer component affects the stability of these particles in serum solutions. In the current study, NLPs assembled with phosphatidylcholine lipids featuring different acyl chain structures were systematically tested to understand the effect that lipid composition has on NLP stability in both neat serum and cell culture media supplemented with 10% serum by volume. The time at which 50% of the particles dissociate, as well as the fraction of the initial population that remains resistant to dissociation, were correlated to key parameters obtained from all-atom simulations of the corresponding lipid bilayers. A significant correlation was observed between the compressibility modulus of the lipid bilayer and particle stability in these complex biological milieu. These results can be used as a reference to tune the stability of these versatile biological nanoparticles for in vitro and in vivo applications.

Original languageEnglish (US)
Pages (from-to)7420-7430
Number of pages11
JournalNanoscale
Volume10
Issue number16
DOIs
StatePublished - Apr 28 2018

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Lipoproteins
HDL Lipoproteins
Lipids
Lipid bilayers
Chemical analysis
Nanoparticles
Proteins
Apolipoproteins
Phospholipids
Scaffolds (biology)
Phosphatidylcholines
Compressibility
Cell culture
Scaffolds
Culture Media
Membrane Proteins
Membranes
Atoms

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Lipid composition dictates serum stability of reconstituted high-density lipoproteins : Implications for: In vivo applications. / Gilmore, Sean F.; Carpenter, Timothy S.; Ingólfsson, Helgi I.; Peters, Sandra K.G.; Henderson, Paul; Blanchette, Craig D.; Fischer, Nicholas O.

In: Nanoscale, Vol. 10, No. 16, 28.04.2018, p. 7420-7430.

Research output: Contribution to journalArticle

Gilmore, Sean F. ; Carpenter, Timothy S. ; Ingólfsson, Helgi I. ; Peters, Sandra K.G. ; Henderson, Paul ; Blanchette, Craig D. ; Fischer, Nicholas O. / Lipid composition dictates serum stability of reconstituted high-density lipoproteins : Implications for: In vivo applications. In: Nanoscale. 2018 ; Vol. 10, No. 16. pp. 7420-7430.
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