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Title: 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.

Authors:
; ; ; ; ; ; ; ; ORCiD logo
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1600087
Grant/Contract Number:  
[SC0012704; 7394; 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:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English

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. doi: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. doi: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 = {2020},
month = {2}
}

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DOI: 10.1073/pnas.1919264117

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