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

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 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.

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1];  [1];  [2];  [1];  [1]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  2. Univ. of California-Davis and UC Davis Comphrehensive Cancer Center, Sacramento, CA (United States)
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA); USDOE Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
1467815
Alternate Identifier(s):
OSTI ID: 1434102
Report Number(s):
LLNL-JRNL-741447
Journal ID: ISSN 2040-3364; NANOHL; 895522
Grant/Contract Number:  
AC52-07NA27344; 15-LW-023; 17-LW-051
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nanoscale
Additional Journal Information:
Journal Volume: 10; Journal Issue: 16; Journal ID: ISSN 2040-3364
Publisher:
Royal Society of Chemistry
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 77 NANOSCIENCE AND NANOTECHNOLOGY

Citation Formats

Gilmore, Sean F., Carpenter, Timothy S., Ingólfsson, Helgi I., Peters, Sandra K. G., Henderson, Paul T., Blanchette, Craig D., and Fischer, Nicholas O.. Lipid composition dictates serum stability of reconstituted high-density lipoproteins: implications for in vivo applications. United States: N. p., 2018. Web. doi:10.1039/C7NR09690A.
Gilmore, Sean F., Carpenter, Timothy S., Ingólfsson, Helgi I., Peters, Sandra K. G., Henderson, Paul T., Blanchette, Craig D., & Fischer, Nicholas O.. Lipid composition dictates serum stability of reconstituted high-density lipoproteins: implications for in vivo applications. United States. doi:10.1039/C7NR09690A.
Gilmore, Sean F., Carpenter, Timothy S., Ingólfsson, Helgi I., Peters, Sandra K. G., Henderson, Paul T., Blanchette, Craig D., and Fischer, Nicholas O.. Wed . "Lipid composition dictates serum stability of reconstituted high-density lipoproteins: implications for in vivo applications". United States. doi:10.1039/C7NR09690A.
@article{osti_1467815,
title = {Lipid composition dictates serum stability of reconstituted high-density lipoproteins: implications for in vivo applications},
author = {Gilmore, Sean F. and Carpenter, Timothy S. and Ingólfsson, Helgi I. and Peters, Sandra K. G. and Henderson, Paul T. and Blanchette, Craig D. and Fischer, Nicholas O.},
abstractNote = {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.},
doi = {10.1039/C7NR09690A},
journal = {Nanoscale},
number = 16,
volume = 10,
place = {United States},
year = {Wed Mar 14 00:00:00 EDT 2018},
month = {Wed Mar 14 00:00:00 EDT 2018}
}

Journal Article:
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This content will become publicly available on March 14, 2019
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