Functional lipid pairs as building blocks of phase-separated membranes
Abstract
Biological membranes exhibit a great deal of compositional and phase heterogeneity due to hundreds of chemically distinct components. As a result, phase separation processes in cell membranes are extremely difficult to study, especially at the molecular level. It is currently believed that the lateral membrane heterogeneity and the formation of domains, or rafts, are driven by lipid–lipid and lipid–protein interactions. Nevertheless, the underlying mechanisms regulating membrane heterogeneity remain poorly understood. In the present work, we combine inelastic X-ray scattering with molecular dynamics simulations to provide direct evidence for the existence of strongly coupled transient lipid pairs. These lipid pairs manifest themselves experimentally through optical vibrational (a.k.a. phononic) modes observed in binary (1,2-dipalmitoyl- sn -glycero-3-phosphocholine [DPPC]–cholesterol) and ternary (DPPC–1,2-dioleoyl- sn -glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-glycero-3-phosphocholine [DOPC/POPC]–cholesterol) systems. The existence of a phononic gap in these vibrational modes is a direct result of the finite size of patches formed by these lipid pairs. The observation of lipid pairs provides a spatial (subnanometer) and temporal (subnanosecond) window into the lipid–lipid interactions in complex mixtures of saturated/unsaturated lipids and cholesterol. Our findings represent a step toward understanding the lateral organization and dynamics of membrane domains using a well-validated probe with a high spatial and temporal resolution.
- Publication Date:
- Research Org.:
- Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1600087
- Alternate Identifier(s):
- OSTI ID: 1607979
- Report Number(s):
- BNL-213789-2020-JAAM
Journal ID: ISSN 0027-8424
- Grant/Contract Number:
- SC0012704; 7394; AC05- 00OR22725; AC05-00OR22725
- Resource Type:
- Published Article
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 117 Journal Issue: 9; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; lipid nanoclusters; phononic gaps; optical phonons; picosecond membranes dynamics; lipid pairs
Citation Formats
Soloviov, Dmytro, Cai, Yong Q., Bolmatov, Dima, Suvorov, Alexey, Zhernenkov, Kirill, Zav’yalov, Dmitry, Bosak, Alexey, Uchiyama, Hiroshi, and Zhernenkov, Mikhail. Functional lipid pairs as building blocks of phase-separated membranes. United States: N. p., 2020.
Web. doi:10.1073/pnas.1919264117.
Soloviov, Dmytro, Cai, Yong Q., Bolmatov, Dima, Suvorov, Alexey, Zhernenkov, Kirill, Zav’yalov, Dmitry, Bosak, Alexey, Uchiyama, Hiroshi, & Zhernenkov, Mikhail. Functional lipid pairs as building blocks of phase-separated membranes. United States. https://doi.org/10.1073/pnas.1919264117
Soloviov, Dmytro, Cai, Yong Q., Bolmatov, Dima, Suvorov, Alexey, Zhernenkov, Kirill, Zav’yalov, Dmitry, Bosak, Alexey, Uchiyama, Hiroshi, and Zhernenkov, Mikhail. Tue .
"Functional lipid pairs as building blocks of phase-separated membranes". United States. https://doi.org/10.1073/pnas.1919264117.
@article{osti_1600087,
title = {Functional lipid pairs as building blocks of phase-separated membranes},
author = {Soloviov, Dmytro and Cai, Yong Q. and Bolmatov, Dima and Suvorov, Alexey and Zhernenkov, Kirill and Zav’yalov, Dmitry and Bosak, Alexey and Uchiyama, Hiroshi and Zhernenkov, Mikhail},
abstractNote = {Biological membranes exhibit a great deal of compositional and phase heterogeneity due to hundreds of chemically distinct components. As a result, phase separation processes in cell membranes are extremely difficult to study, especially at the molecular level. It is currently believed that the lateral membrane heterogeneity and the formation of domains, or rafts, are driven by lipid–lipid and lipid–protein interactions. Nevertheless, the underlying mechanisms regulating membrane heterogeneity remain poorly understood. In the present work, we combine inelastic X-ray scattering with molecular dynamics simulations to provide direct evidence for the existence of strongly coupled transient lipid pairs. These lipid pairs manifest themselves experimentally through optical vibrational (a.k.a. phononic) modes observed in binary (1,2-dipalmitoyl- sn -glycero-3-phosphocholine [DPPC]–cholesterol) and ternary (DPPC–1,2-dioleoyl- sn -glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-glycero-3-phosphocholine [DOPC/POPC]–cholesterol) systems. The existence of a phononic gap in these vibrational modes is a direct result of the finite size of patches formed by these lipid pairs. The observation of lipid pairs provides a spatial (subnanometer) and temporal (subnanosecond) window into the lipid–lipid interactions in complex mixtures of saturated/unsaturated lipids and cholesterol. Our findings represent a step toward understanding the lateral organization and dynamics of membrane domains using a well-validated probe with a high spatial and temporal resolution.},
doi = {10.1073/pnas.1919264117},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 9,
volume = 117,
place = {United States},
year = {Tue Feb 18 00:00:00 EST 2020},
month = {Tue Feb 18 00:00:00 EST 2020}
}
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https://doi.org/10.1073/pnas.1919264117
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