Functional lipid pairs as building blocks of phase-separated membranes

Soloviov, Dmytro; Cai, Yong Q.; Bolmatov, Dima; Suvorov, Alexey; Zhernenkov, Kirill; Zav’yalov, Dmitry; Bosak, Alexey; Uchiyama, Hiroshi; Zhernenkov, Mikhail

doi:10.1073/pnas.1919264117

Functional lipid pairs as building blocks of phase-separated membranes

Journal Article · Mon Feb 17 23:00:00 EST 2020 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1919264117· OSTI ID:1600087

Soloviov, Dmytro; Cai, Yong Q.; Bolmatov, Dima; Suvorov, Alexey; Zhernenkov, Kirill; Zav’yalov, Dmitry; Bosak, Alexey; Uchiyama, Hiroshi;

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.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0012704; AC05-00OR22725

OSTI ID:: 1600087

Alternate ID(s):: OSTI ID: 1607979

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 9 Vol. 117; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

References (69)

Lipid Raft Formation: Key Role of Polyunsaturated Phospholipids Wang, Chang; Yu, Yuming; Regen, Steven L. Angewandte Chemie International Edition, Vol. 56, Issue 6 https://doi.org/10.1002/anie.201611367	journal	January 2017
Ultrafast Vibrational Dynamics of Membrane-Bound Peptides at the Lipid Bilayer/Water Interface Tan, Junjun; Zhang, Baixiong; Luo, Yi Angewandte Chemie International Edition, Vol. 56, Issue 42 https://doi.org/10.1002/anie.201706996	journal	September 2017
Selective solubilization of proteins and phospholipids from red blood cell membranes by nonionic detergents Yu, John; Fischman, Donald A.; Steck, Theodore L. Journal of Supramolecular Structure, Vol. 1, Issue 3 https://doi.org/10.1002/jss.400010308	journal	January 1973
Phase equilibria in the phosphatidylcholine-cholesterol system Hjort Ipsen, J.; Karlström, G.; Mourtisen, O. G. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 905, Issue 1 https://doi.org/10.1016/0005-2736(87)90020-4	journal	November 1987
Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface Brown, Deborah A.; Rose, John K. Cell, Vol. 68, Issue 3 https://doi.org/10.1016/0092-8674(92)90189-J	journal	February 1992
Condensed complexes of cholesterol and phospholipids McConnell, Harden M.; Radhakrishnan, Arun Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1610, Issue 2 https://doi.org/10.1016/S0005-2736(03)00015-4	journal	March 2003
Collective Chain Dynamics in Lipid Bilayers by Inelastic X-Ray Scattering Weiss, Thomas M.; Chen, Poe-Jou; Sinn, Harald Biophysical Journal, Vol. 84, Issue 6 https://doi.org/10.1016/S0006-3495(03)75105-4	journal	June 2003
Structure of gel phase saturated lecithin bilayers: temperature and chain length dependence Sun, W. J.; Tristram-Nagle, S.; Suter, R. M. Biophysical Journal, Vol. 71, Issue 2 https://doi.org/10.1016/S0006-3495(96)79290-1	journal	August 1996
Condensed Complexes of Cholesterol and Phospholipids Radhakrishnan, Arun; McConnell, Harden M. Biophysical Journal, Vol. 77, Issue 3 https://doi.org/10.1016/S0006-3495(99)76998-5	journal	September 1999
A Microscopic Interaction Model of Maximum Solubility of Cholesterol in Lipid Bilayers Huang, Juyang; Feigenson, Gerald W. Biophysical Journal, Vol. 76, Issue 4 https://doi.org/10.1016/S0006-3495(99)77369-8	journal	April 1999
An X-ray scattering beamline for studying dynamics Baron, A. Q. R.; Tanaka, Y.; Goto, S. Journal of Physics and Chemistry of Solids, Vol. 61, Issue 3 https://doi.org/10.1016/S0022-3697(99)00337-6	journal	March 2000
Unified phonon-based approach to the thermodynamics of solid, liquid and gas states Bolmatov, Dima; Zav’yalov, Dmitry; Zhernenkov, Mikhail Annals of Physics, Vol. 363 https://doi.org/10.1016/j.aop.2015.09.018	journal	December 2015
Thermodynamics of lipid interactions in complex bilayers Almeida, Paulo F. F. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1788, Issue 1 https://doi.org/10.1016/j.bbamem.2008.08.007	journal	January 2009
Lipid lateral diffusion and membrane heterogeneity Lindblom, Göran; Orädd, Greger Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1788, Issue 1 https://doi.org/10.1016/j.bbamem.2008.08.016	journal	January 2009
Crossover from picosecond collective to single particle dynamics defines the mechanism of lateral lipid diffusion Bolmatov, Dima; Cai, Yong Q.; Zav’yalov, Dmitry Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1860, Issue 11 https://doi.org/10.1016/j.bbamem.2018.07.004	journal	November 2018
Minimal Model of Plasma Membrane Heterogeneity Requires Coupling Cortical Actin to Criticality Machta, Benjamin B.; Papanikolaou, Stefanos; Sethna, James P. Biophysical Journal, Vol. 100, Issue 7 https://doi.org/10.1016/j.bpj.2011.02.029	journal	April 2011
Water Adsorption Isotherms of Lipids Marsh, Derek Biophysical Journal, Vol. 101, Issue 11 https://doi.org/10.1016/j.bpj.2011.10.031	journal	December 2011
Polyunsaturated Lipids Regulate Membrane Domain Stability by Tuning Membrane Order Levental, Kandice R.; Lorent, Joseph H.; Lin, Xubo Biophysical Journal, Vol. 110, Issue 8 https://doi.org/10.1016/j.bpj.2016.03.012	journal	April 2016
The Continuing Mystery of Lipid Rafts Levental, Ilya; Veatch, Sarah L. Journal of Molecular Biology, Vol. 428, Issue 24 https://doi.org/10.1016/j.jmb.2016.08.022	journal	December 2016
Ras trafficking, localization and compartmentalized signalling Prior, Ian A.; Hancock, John F. Seminars in Cell & Developmental Biology, Vol. 23, Issue 2 https://doi.org/10.1016/j.semcdb.2011.09.002	journal	April 2012
Biophysical properties of lipids and dynamic membranes Janmey, P. A.; Kinnunen, P. K. J. Trends in Cell Biology, Vol. 16, Issue 10 https://doi.org/10.1016/j.tcb.2006.08.009	journal	October 2006
Principles of the Theory of Solids Ziman, J. M. https://doi.org/10.1017/CBO9781139644075	book	January 1972
Membrane Lipid Nanodomains Cebecauer, Marek; Amaro, Mariana; Jurkiewicz, Piotr Chemical Reviews, Vol. 118, Issue 23 https://doi.org/10.1021/acs.chemrev.8b00322	journal	October 2018
Biological Membrane Organization and Cellular Signaling Cheng, Xiaolin; Smith, Jeremy C. Chemical Reviews, Vol. 119, Issue 9 https://doi.org/10.1021/acs.chemrev.8b00439	journal	January 2019
Terasonic Excitations in 2D Gold Nanoparticle Arrays in a Water Matrix as Revealed by Atomistic Simulations Bolmatov, Dima; Zhernenkov, Mikhail; Zav’yalov, Dmitry The Journal of Physical Chemistry C, Vol. 120, Issue 35 https://doi.org/10.1021/acs.jpcc.6b08250	journal	August 2016
Revealing the Mechanism of the Viscous-to-Elastic Crossover in Liquids Bolmatov, Dima; Zhernenkov, Mikhail; Zav’yalov, Dmitry The Journal of Physical Chemistry Letters, Vol. 6, Issue 15 https://doi.org/10.1021/acs.jpclett.5b01338	journal	July 2015
Multiple Interacting Collective Modes and Phonon Gap in Phospholipid Membranes D’Angelo, Giovanna; Nibali, Valeria Conti; Wanderlingh, Ulderico The Journal of Physical Chemistry Letters, Vol. 9, Issue 15 https://doi.org/10.1021/acs.jpclett.8b01658	journal	July 2018
Crowding-Induced Mixing Behavior of Lipid Bilayers: Examination of Mixing Energy, Phase, Packing Geometry, and Reversibility Zeno, Wade F.; Rystov, Alice; Sasaki, Darryl Y. Langmuir, Vol. 32, Issue 18 https://doi.org/10.1021/acs.langmuir.6b00831	journal	April 2016
How to Determine Lipid Interactions in Membranes from Experiment Through the Ising Model Almeida, Paulo F. Langmuir, Vol. 35, Issue 1 https://doi.org/10.1021/acs.langmuir.8b03054	journal	December 2018
Emergent Optical Phononic Modes upon Nanoscale Mesogenic Phase Transitions Bolmatov, Dima; Zhernenkov, Mikhail; Sharpnack, Lewis Nano Letters, Vol. 17, Issue 6 https://doi.org/10.1021/acs.nanolett.7b01324	journal	May 2017
The Molecular Structure of the Liquid-Ordered Phase of Lipid Bilayers Sodt, Alexander J.; Sandar, Michael Logan; Gawrisch, Klaus Journal of the American Chemical Society, Vol. 136, Issue 2 https://doi.org/10.1021/ja4105667	journal	January 2014
Push and Pull Forces in Lipid Raft Formation: The Push Can Be as Important as the Pull Wang, Chang; Krause, Martin R.; Regen, Steven L. Journal of the American Chemical Society, Vol. 137, Issue 2 https://doi.org/10.1021/ja5115437	journal	January 2015
Simulation of the l _o −l _d Phase Boundary in DSPC/DOPC/Cholesterol Ternary Mixtures Using Pairwise Interactions Dai, Jian; Alwarawrah, Mohammad; Ali, Md Rejwan The Journal of Physical Chemistry B, Vol. 115, Issue 7 https://doi.org/10.1021/jp110243v	journal	February 2011
Preparation of Solid-Supported Lipid Bilayers by Spin-Coating Mennicke, Ulrike; Salditt, Tim Langmuir, Vol. 18, Issue 21 https://doi.org/10.1021/la025863f	journal	October 2002
Push–Pull Mechanism for Lipid Raft Formation Krause, Martin R.; Daly, Trevor A.; Almeida, Paulo F. Langmuir, Vol. 30, Issue 12 https://doi.org/10.1021/la500510s	journal	March 2014
GPI-anchored proteins are organized in submicron domains at the cell surface Varma, Rajat; Mayor, Satyajit Nature, Vol. 394, Issue 6695 https://doi.org/10.1038/29563	journal	August 1998
Functional rafts in cell membranes Simons, Kai; Ikonen, Elina Nature, Vol. 387, Issue 6633 https://doi.org/10.1038/42408	journal	June 1997
Direct observation of the nanoscale dynamics of membrane lipids in a living cell Eggeling, Christian; Ringemann, Christian; Medda, Rebecca Nature, Vol. 457, Issue 7233 https://doi.org/10.1038/nature07596	journal	December 2008
Allosteric regulation of G protein–coupled receptor activity by phospholipids Dawaliby, Rosie; Trubbia, Cataldo; Delporte, Cédric Nature Chemical Biology, Vol. 12, Issue 1 https://doi.org/10.1038/nchembio.1960	journal	November 2015
Revealing the mechanism of passive transport in lipid bilayers via phonon-mediated nanometre-scale density fluctuations Zhernenkov, Mikhail; Bolmatov, Dima; Soloviov, Dmitry Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms11575	journal	May 2016
The mystery of membrane organization: composition, regulation and roles of lipid rafts Sezgin, Erdinc; Levental, Ilya; Mayor, Satyajit Nature Reviews Molecular Cell Biology, Vol. 18, Issue 6 https://doi.org/10.1038/nrm.2017.16	journal	March 2017
Membrane lipids: where they are and how they behave van Meer, Gerrit; Voelker, Dennis R.; Feigenson, Gerald W. Nature Reviews Molecular Cell Biology, Vol. 9, Issue 2 https://doi.org/10.1038/nrm2330	journal	February 2008
Ultrafast energy relaxation dynamics of amide I vibrations coupled with protein-bound water molecules Tan, Junjun; Zhang, Jiahui; Li, Chuanzhao Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-08899-3	journal	March 2019
Thermally triggered phononic gaps in liquids at THz scale Bolmatov, Dima; Zhernenkov, Mikhail; Zav’yalov, Dmitry Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep19469	journal	January 2016
Pair interactions among ternary DPPC/POPC/cholesterol mixtures in liquid-ordered and liquid-disordered phases Yang, Jing; Martí, Jordi; Calero, Carles Soft Matter, Vol. 12, Issue 20 https://doi.org/10.1039/C6SM00345A	journal	January 2016
Perspective on the Martini model Marrink, Siewert J.; Tieleman, D. Peter Chemical Society Reviews, Vol. 42, Issue 16 https://doi.org/10.1039/c3cs60093a	journal	January 2013
FLIM-FRET and FRAP reveal association of influenza virus haemagglutinin with membrane rafts Engel, Stephanie; Scolari, Silvia; Thaa, Bastian Biochemical Journal, Vol. 425, Issue 3 https://doi.org/10.1042/BJ20091388	journal	January 2010
Large-scale fluid/fluid phase separation of proteins and lipids in giant plasma membrane vesicles Baumgart, T.; Hammond, A. T.; Sengupta, P. Proceedings of the National Academy of Sciences, Vol. 104, Issue 9 https://doi.org/10.1073/pnas.0611357104	journal	February 2007
Critical fluctuations in domain-forming lipid mixtures Veatch, S. L.; Soubias, O.; Keller, S. L. Proceedings of the National Academy of Sciences, Vol. 104, Issue 45 https://doi.org/10.1073/pnas.0703513104	journal	October 2007
Dynamic clustered distribution of hemagglutinin resolved at 40 nm in living cell membranes discriminates between raft theories Hess, S. T.; Gould, T. J.; Gudheti, M. V. Proceedings of the National Academy of Sciences, Vol. 104, Issue 44 https://doi.org/10.1073/pnas.0708066104	journal	October 2007
Protein area occupancy at the center of the red blood cell membrane Dupuy, A. D.; Engelman, D. M. Proceedings of the National Academy of Sciences, Vol. 105, Issue 8 https://doi.org/10.1073/pnas.0712379105	journal	February 2008
Plasma membranes are poised for activation of raft phase coalescence at physiological temperature Lingwood, D.; Ries, J.; Schwille, P. Proceedings of the National Academy of Sciences, Vol. 105, Issue 29 https://doi.org/10.1073/pnas.0804374105	journal	July 2008
Bile Acids Modulate Signaling by Functional Perturbation of Plasma Membrane Domains Zhou, Yong; Maxwell, Kelsey N.; Sezgin, Erdinc Journal of Biological Chemistry, Vol. 288, Issue 50 https://doi.org/10.1074/jbc.M113.519116	journal	October 2013
Sorting of sphingolipids in epithelial (Madin-Darby canine kidney) cells. van Meer, G.; Stelzer, E. H.; Wijnaendts-van-Resandt, R. W. The Journal of Cell Biology, Vol. 105, Issue 4 https://doi.org/10.1083/jcb.105.4.1623	journal	October 1987
Universal disorder-induced broadening of phonon bands: from disordered lattices to glasses Bouchbinder, Eran; Lerner, Edan New Journal of Physics, Vol. 20, Issue 7 https://doi.org/10.1088/1367-2630/aacef4	journal	July 2018
Phase Separation in Lipid Membranes Heberle, F. A.; Feigenson, G. W. Cold Spring Harbor Perspectives in Biology, Vol. 3, Issue 4 https://doi.org/10.1101/cshperspect.a004630	journal	March 2011
Order and disorder in fully hydrated unoriented bilayers of gel-phase dipalmitoylphosphatidylcholine Sun, W. -J.; Suter, R. M.; Knewtson, M. A. Physical Review E, Vol. 49, Issue 5 https://doi.org/10.1103/PhysRevE.49.4665	journal	May 1994
Molecular dynamics simulation of short-wavelength collective dynamics of phospholipid membranes Conti Nibali, Valeria; D'Angelo, Giovanna; Tarek, Mounir Physical Review E, Vol. 89, Issue 5 https://doi.org/10.1103/PhysRevE.89.050301	journal	May 2014
Ordered Nanoclusters in Lipid-Cholesterol Membranes Ratajczak, Maria K.; Chi, Eva Y.; Frey, Shelli L. Physical Review Letters, Vol. 103, Issue 2 https://doi.org/10.1103/PhysRevLett.103.028103	journal	July 2009
Cholesterol-Phospholipid Interactions: New Insights from Surface X-Ray Scattering Data Ivankin, Andrey; Kuzmenko, Ivan; Gidalevitz, David Physical Review Letters, Vol. 104, Issue 10 https://doi.org/10.1103/PhysRevLett.104.108101	journal	March 2010
Collective Dynamics in Fully Hydrated Phospholipid Bilayers Studied by Inelastic X-Ray Scattering Chen, S. H.; Liao, C. Y.; Huang, H. W. Physical Review Letters, Vol. 86, Issue 4 https://doi.org/10.1103/PhysRevLett.86.740	journal	January 2001
Miscibility Phase Diagrams of Giant Vesicles Containing Sphingomyelin Veatch, Sarah L.; Keller, Sarah L. Physical Review Letters, Vol. 94, Issue 14 https://doi.org/10.1103/PhysRevLett.94.148101	journal	April 2005
Soft Matter in Lipid–Protein Interactions Brown, Michael F. Annual Review of Biophysics, Vol. 46, Issue 1 https://doi.org/10.1146/annurev-biophys-070816-033843	journal	May 2017
The Observation of Highly Ordered Domains in Membranes with Cholesterol Armstrong, Clare L.; Marquardt, Drew; Dies, Hannah PLoS ONE, Vol. 8, Issue 6 https://doi.org/10.1371/journal.pone.0066162	journal	June 2013
Proving Lipid Rafts Exist: Membrane Domains in the Prokaryote Borrelia burgdorferi Have the Same Properties as Eukaryotic Lipid Rafts LaRocca, Timothy J.; Pathak, Priyadarshini; Chiantia, Salvatore PLoS Pathogens, Vol. 9, Issue 5 https://doi.org/10.1371/journal.ppat.1003353	journal	May 2013
Areas of Molecules in Membranes Consisting of Mixtures Edholm, Olle; Nagle, John F. Biophysical Journal, Vol. 89, Issue 3 https://doi.org/10.1529/biophysj.105.064329	journal	September 2005
The Condensing Effect of Cholesterol in Lipid Bilayers Hung, Wei-Chin; Lee, Ming-Tao; Chen, Fang-Yu Biophysical Journal, Vol. 92, Issue 11 https://doi.org/10.1529/biophysj.106.099234	journal	June 2007
Line Tensions, Correlation Lengths, and Critical Exponents in Lipid Membranes Near Critical Points Honerkamp-Smith, Aurelia R.; Cicuta, Pietro; Collins, Marcus D. Biophysical Journal, Vol. 95, Issue 1 https://doi.org/10.1529/biophysj.107.128421	journal	July 2008
Crystallization around solid-like nanosized docks can explain the specificity, diversity, and stability of membrane microdomains de Almeida, Rodrigo F. M.; Joly, Etienne Frontiers in Plant Science, Vol. 5 https://doi.org/10.3389/fpls.2014.00072	journal	March 2014

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