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 T.; Blanchette, Craig D.; Fischer, Nicholas O.

doi:10.1039/C7NR09690A

Title: Lipid composition dictates serum stability of reconstituted high-density lipoproteins: implications for in vivo applications

Journal Article · Wed Mar 14 00:00:00 EDT 2018 · Nanoscale

DOI:https://doi.org/10.1039/C7NR09690A· OSTI ID:1467815

^[1];

^[1]; Peters, Sandra K. G. ^[1]; Henderson, Paul T. ^[2]; Blanchette, Craig D. ^[1]; Fischer, Nicholas O. ^[1]

Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Univ. of California-Davis and UC Davis Comphrehensive Cancer Center, Sacramento, CA (United States)

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 studies 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.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA); USDOE Laboratory Directed Research and Development (LDRD) Program

Grant/Contract Number:: AC52-07NA27344; 15-LW-023; 17-LW-051

OSTI ID:: 1467815

Alternate ID(s):: OSTI ID: 1434102

Report Number(s):: LLNL-JRNL-741447; NANOHL; 895522

Journal Information:: Nanoscale, Vol. 10, Issue 16; ISSN 2040-3364

Publisher:: Royal Society of ChemistryCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 11 works

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