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 language | English (US) |
|---|---|
| Pages (from-to) | 7420-7430 |
| Number of pages | 11 |
| Journal | Nanoscale |
| Volume | 10 |
| Issue number | 16 |
| DOIs | |
| State | Published - Apr 28 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Lipid composition dictates serum stability of reconstituted high-density lipoproteins
T2 - Implications for: In vivo applications
AU - Gilmore, Sean F.
AU - Carpenter, Timothy S.
AU - Ingólfsson, Helgi I.
AU - Peters, Sandra K.G.
AU - Henderson, Paul
AU - Blanchette, Craig D.
AU - Fischer, Nicholas O
PY - 2018/4/28
Y1 - 2018/4/28
N2 - 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.
AB - 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.
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U2 - 10.1039/c7nr09690a
DO - 10.1039/c7nr09690a
M3 - Article
VL - 10
SP - 7420
EP - 7430
JO - Nanoscale
JF - Nanoscale
SN - 2040-3364
IS - 16
ER -