Peptide-Induced Lipid Flip-Flop in Asymmetric Liposomes Measured by Small Angle Neutron Scattering

Nguyen, Michael H. L.; DiPasquale, Mitchell; Rickeard, Brett W.; Doktorova, Milka; Heberle, Frederick A.; Scott, Haden L.; Barrera, Francisco N.; Taylor, Graham; Collier, Charles P.; Stanley, Christopher B.; Katsaras, John; Marquardt, Drew

doi:10.1021/acs.langmuir.9b01625

Title: Peptide-Induced Lipid Flip-Flop in Asymmetric Liposomes Measured by Small Angle Neutron Scattering

Journal Article · Tue Aug 13 00:00:00 EDT 2019 · Langmuir

DOI:https://doi.org/10.1021/acs.langmuir.9b01625· OSTI ID:1561589

Nguyen, Michael H. L. ^[1]; DiPasquale, Mitchell ^[1]; Rickeard, Brett W. ^[1]; Doktorova, Milka ^[2];

^[3]; Scott, Haden L. ^[4]; Barrera, Francisco N. ^[4]; Taylor, Graham ^[4];

^[5];

^[6];

^[7];

^[1]

Univ. of Windsor, Windsor, ON (Canada)
Univ. of Texas Health Science Center at Houston, Houston, TX (United States)
Univ. of Texas Health Science Center at Houston, Houston, TX (United States); Univ. of Tennessee, Knoxville, TN (United States)
Univ. of Tennessee, Knoxville, TN (United States)
Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)

Despite the prevalence of lipid transbilayer asymmetry in natural plasma membranes, most biomimetic model membranes studied are symmetric. Recent advances have helped to overcome the difficulties in preparing asymmetric liposomes in vitro, allowing for the examination of a larger set of relevant biophysical questions. Here, we investigate the stability of asymmetric bilayers by measuring lipid flip-flop with time-resolved small-angle neutron scattering (SANS). Asymmetric large unilamellar vesicles with inner bilayer leaflets containing predominantly 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and outer leaflets composed mainly of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) displayed slow spontaneous flip-flop at 37 °C (half-time, t_1/2 = 140 h). However, inclusion of peptides, namely, gramicidin, alamethicin, melittin, or pHLIP (i.e., pH-low insertion peptide), accelerated lipid flip-flop. For three of these peptides (i.e., pHLIP, alamethicin, and melittin), each of which was added externally to preformed asymmetric vesicles, we observed a completely scrambled bilayer in less than 2 h. Gramicidin, on the other hand, was preincorporated during the formation of the asymmetric liposomes and showed a time resolvable 8-fold increase in the rate of lipid asymmetry loss. These results point to a membrane surface-related (e.g., adsorption/insertion) event as the primary driver of lipid scrambling in the asymmetric model membranes of this study. Here, we discuss the implications of membrane peptide binding, conformation, and insertion on lipid asymmetry.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1561589

Journal Information:: Langmuir, Vol. 35, Issue 36; ISSN 0743-7463

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 31 works

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