Protein Crowding and Cholesterol Increase Cell Membrane Viscosity in a Temperature Dependent Manner
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
37071435
PubMed Central
PMC10173458
DOI
10.1021/acs.jctc.3c00060
Knihovny.cz E-zdroje
- MeSH
- buněčná membrána metabolismus MeSH
- difuze MeSH
- lipidové dvojvrstvy metabolismus MeSH
- lipidy * MeSH
- simulace molekulární dynamiky * MeSH
- teplota MeSH
- viskozita MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- lipidové dvojvrstvy MeSH
- lipidy * MeSH
Shear viscosity of lipid membranes dictates how fast lipids, proteins, and other membrane constituents travel along the membrane and rotate around their principal axis, thus governing the rates of diffusion-limited reactions taking place at membranes. In this framework, the heterogeneity of biomembranes indicates that cells could regulate these rates via varying local viscosities. Unfortunately, experiments to probe membrane viscosity under various conditions are tedious and error prone. Molecular dynamics simulations provide an attractive alternative, especially given that recent theoretical developments enable the elimination of finite-size effects in simulations. Here, we use a variety of different equilibrium methods to extract the shear viscosities of lipid membranes from both coarse-grained and all-atom molecular dynamics simulations. We systematically probe the variables relevant for cellular membranes, namely, membrane protein crowding, cholesterol concentration, and the length and saturation level of lipid acyl chains, as well as temperature. Our results highlight that in their physiologically relevant ranges, protein concentration, cholesterol concentration, and temperature have significantly larger effects on membrane viscosity than lipid acyl chain length and unsaturation level. In particular, the crowding with proteins has a significant effect on the shear viscosity of lipid membranes and thus on the diffusion occurring in the membranes. Our work also provides the largest collection of membrane viscosity values from simulation to date, which can be used by the community to predict the diffusion coefficients or their trends via the Saffman-Delbrück description. Additionally, it is worth emphasizing that diffusion coefficients extracted from simulations exploiting periodic boundary conditions must be corrected for the finite-size effects prior to comparison with experiment, for which the present collection of viscosity values can readily be used. Finally, our thorough comparison to experiments suggests that there is room for improvement in the description of bilayer dynamics provided by the present force fields.
Computational Physics Laboratory Tampere University FI 33720 Tampere Finland
Department of Physics University of Helsinki FI 00560 Helsinki Finland
Institute of Biotechnology University of Helsinki FI 00790 Helsinki Finland
Zobrazit více v PubMed
Gupta K.; Donlan J. A.; Hopper J. T.; Uzdavinys P.; Landreh M.; Struwe W. B.; Drew D.; Baldwin A. J.; Stansfeld P. J.; Robinson C. V. The role of interfacial lipids in stabilizing membrane protein oligomers. Nature 2017, 541, 421.10.1038/nature20820. PubMed DOI PMC
Scarselli M.; Annibale P.; McCormick P. J.; Kolachalam S.; Aringhieri S.; Radenovic A.; Corsini G. U.; Maggio R. Revealing G-protein-coupled receptor oligomerization at the single-molecule level through a nanoscopic lens: methods, dynamics and biological function. FEBS J. 2016, 283, 1197–1217. 10.1111/febs.13577. PubMed DOI
Gahbauer S.; Böckmann R. A. Membrane-mediated oligomerization of G protein coupled receptors and its implications for GPCR function. Front. Physiol. 2016, 7, 494.10.3389/fphys.2016.00494. PubMed DOI PMC
Adrien V.; Rayan G.; Astafyeva K.; Broutin I.; Picard M.; Fuchs P.; Urbach W.; Taulier N. How to best estimate the viscosity of lipid bilayers. Biophys. Chem. 2022, 281, 106732.10.1016/j.bpc.2021.106732. PubMed DOI
Chen Y.; Lagerholm B. C.; Yang B.; Jacobson K. Methods to measure the lateral diffusion of membrane lipids and proteins. Methods 2006, 39, 147–153. 10.1016/j.ymeth.2006.05.008. PubMed DOI
Gurtovenko A. A.; Javanainen M.; Lolicato F.; Vattulainen I. The devil is in the details: what do we really track in single-particle tracking experiments of diffusion in biological membranes?. J. Phys. Chem. Lett. 2019, 10, 1005–1011. 10.1021/acs.jpclett.9b00065. PubMed DOI
Mobarak E.; Javanainen M.; Kulig W.; Honigmann A.; Sezgin E.; Aho N.; Eggeling C.; Rog T.; Vattulainen I. How to minimize dye-induced perturbations while studying biomembrane structure and dynamics: PEG linkers as a rational alternative. Biochim. Biophys. Acta 2018, 1860, 2436–2445. 10.1016/j.bbamem.2018.07.003. PubMed DOI
Javanainen M.; Ollila O. S.; Martinez-Seara H. Rotational diffusion of membrane proteins in crowded membranes. J. Phys. Chem. B 2020, 124, 2994–3001. 10.1021/acs.jpcb.0c00884. PubMed DOI
Peters R.; Cherry R. J. Lateral and rotational diffusion of bacteriorhodopsin in lipid bilayers: experimental test of the Saffman-Delbrück equations. Proc. Natl. Acad. Sci. U.S.A. 1982, 79, 4317–4321. 10.1073/pnas.79.14.4317. PubMed DOI PMC
James Z. M.; McCaffrey J. E.; Torgersen K. D.; Karim C. B.; Thomas D. D. Protein-protein interactions in calcium transport regulation probed by saturation transfer electron paramagnetic resonance. Biophys. J. 2012, 103, 1370–1378. 10.1016/j.bpj.2012.08.032. PubMed DOI PMC
Saffman P.; Delbrück M. Brownian motion in biological membranes. Proc. Natl. Acad. Sci. U.S.A. 1975, 72, 3111–3113. 10.1073/pnas.72.8.3111. PubMed DOI PMC
Saffman P. Brownian motion in thin sheets of viscous fluid. J. Fluid Mech. 1976, 73, 593–602. 10.1017/S0022112076001511. DOI
Ramadurai S.; Holt A.; Krasnikov V.; van den Bogaart G.; Killian J. A.; Poolman B. Lateral diffusion of membrane proteins. J. Am. Chem. Soc. 2009, 131, 12650–12656. 10.1021/ja902853g. PubMed DOI
Vaz W. L.; Goodsaid-Zalduondo F.; Jacobson K. Lateral diffusion of lipids and proteins in bilayer membranes. FEBS Lett. 1984, 174, 199–207. 10.1016/0014-5793(84)81157-6. DOI
Weiß K.; Neef A.; Van Q.; Kramer S.; Gregor I.; Enderlein J. Quantifying the diffusion of membrane proteins and peptides in black lipid membranes with 2-focus fluorescence correlation spectroscopy. Biophys. J. 2013, 105, 455–462. 10.1016/j.bpj.2013.06.004. PubMed DOI PMC
Oswald F.; Varadarajan A.; Lill H.; Peterman E. J.; Bollen Y. J. MreB-dependent organization of the E. Coli cytoplasmic membrane controls membrane protein diffusion. Biophys. J. 2016, 110, 1139–1149. 10.1016/j.bpj.2016.01.010. PubMed DOI PMC
Javanainen M.; Martinez-Seara H.; Metzler R.; Vattulainen I. Diffusion of integral membrane proteins in protein-rich membranes. J. Phys. Chem. Lett. 2017, 8, 4308–4313. 10.1021/acs.jpclett.7b01758. PubMed DOI
Goose J. E.; Sansom M. S. Reduced lateral mobility of lipids and proteins in crowded membranes. PLoS Comp. Biol. 2013, 9, e100303310.1371/journal.pcbi.1003033. PubMed DOI PMC
Guigas G.; Weiss M. Size-dependent diffusion of membrane inclusions. Biophys. J. 2006, 91, 2393–2398. 10.1529/biophysj.106.087031. PubMed DOI PMC
Petrov E. P.; Schwille P. Translational diffusion in lipid membranes beyond the Saffman-Delbrück approximation. Biophys. J. 2008, 94, L41–L43. 10.1529/biophysj.107.126565. PubMed DOI PMC
Petrov E. P.; Petrosyan R.; Schwille P. Translational and rotational diffusion of micrometer-sized solid domains in lipid membranes. Soft Matter 2012, 8, 7552–7555. 10.1039/c2sm25796c. DOI
Faizi H. A.; Dimova R.; Vlahovska P. M. A vesicle microrheometer for high-throughput viscosity measurements of lipid and polymer membranes. Biophys. J. 2022, 121, 910–918. 10.1016/j.bpj.2022.02.015. PubMed DOI PMC
Jahl P. E.; Parthasarathy R. Assessing the use of ellipsoidal microparticles for determining lipid membrane viscosity. Biophys. J. 2021, 120, 5513–5520. 10.1016/j.bpj.2021.11.020. PubMed DOI PMC
Nojima Y.; Iwata K. Viscosity heterogeneity inside lipid bilayers of single-component phosphatidylcholine liposomes observed with picosecond time-resolved fluorescence spectroscopy. J. Phys. Chem. B 2014, 118, 8631–8641. 10.1021/jp503921e. PubMed DOI
Chakraborty S.; Doktorova M.; Molugu T. R.; Heberle F. A.; Scott H. L.; Dzikovski B.; Nagao M.; Stingaciu L.-R.; Standaert R. F.; Barrera F. N.; et al. How cholesterol stiffens unsaturated lipid membranes. Proc. Natl. Acad. Sci. U.S.A. 2020, 117, 21896–21905. 10.1073/pnas.2004807117. PubMed DOI PMC
Spille J.-H.; Zürn A.; Hoffmann C.; Lohse M. J.; Harms G. S. Rotational diffusion of the α2a adrenergic receptor revealed by FlAsH labeling in living cells. Biophys. J. 2011, 100, 1139–1148. 10.1016/j.bpj.2010.08.080. PubMed DOI PMC
Roos M.; Ott M.; Hofmann M.; Link S.; Rössler E.; Balbach J.; Krushelnitsky A.; Saalwächter K. Coupling and decoupling of rotational and translational diffusion of proteins under crowding conditions. J. Am. Chem. Soc. 2016, 138, 10365–10372. 10.1021/jacs.6b06615. PubMed DOI
Hormel T. T.; Kurihara S. Q.; Brennan M. K.; Wozniak M. C.; Parthasarathy R. Measuring lipid membrane viscosity using rotational and translational probe diffusion. Phys. Rev. Lett. 2014, 112, 188101.10.1103/PhysRevLett.112.188101. PubMed DOI
Camley B. A.; Lerner M. G.; Pastor R. W.; Brown F. L. Strong influence of periodic boundary conditions on lateral diffusion in lipid bilayer membranes. J. Chem. Phys. 2015, 143, 243113.10.1063/1.4932980. PubMed DOI PMC
Venable R. M.; Ingólfsson H. I.; Lerner M. G.; Perrin B. S.; Camley B. A.; Marrink S. J.; Brown F. L. H.; Pastor R. W. Lipid and peptide diffusion in bilayers: the Saffman-Delbrück model and periodic boundary conditions. J. Phys. Chem. B 2017, 121, 3443.10.1021/acs.jpcb.6b09111. PubMed DOI PMC
Vögele M.; Hummer G. Divergent diffusion coefficients in simulations of fluids and lipid membranes. J. Phys. Chem. B 2016, 120, 8722–8732. 10.1021/acs.jpcb.6b05102. PubMed DOI
Vögele M.; Köfinger J.; Hummer G. Hydrodynamics of diffusion in lipid membrane simulations. Phys. Rev. Lett. 2018, 120, 268104.10.1103/PhysRevLett.120.268104. PubMed DOI
Vögele M.; Koefinger J.; Hummer G. Finite-size corrected rotational diffusion coefficients of membrane proteins and carbon nanotubes from molecular dynamics simulations. J. Phys. Chem. B 2019, 123, 5099.10.1021/acs.jpcb.9b01656. PubMed DOI PMC
Yeh I.-C.; Hummer G. System-size dependence of diffusion coefficients and viscosities from molecular dynamics simulations with periodic boundary conditions. J. Phys. Chem. B 2004, 108, 15873–15879. 10.1021/jp0477147. DOI
Linke M.; Köfinger J.; Hummer G. Rotational diffusion depends on box size in molecular dynamics simulations. J. Phys. Chem. Lett. 2018, 9, 2874–2878. 10.1021/acs.jpclett.8b01090. PubMed DOI
Den Otter W.; Shkulipa S. Intermonolayer friction and surface shear viscosity of lipid bilayer membranes. Biophys. J. 2007, 93, 423–433. 10.1529/biophysj.107.105395. PubMed DOI PMC
Zgorski A.; Pastor R. W.; Lyman E. Surface shear viscosity and interleaflet friction from nonequilibrium simulations of lipid bilayers. J. Chem. Theory Comput. 2019, 15, 6471–6481. 10.1021/acs.jctc.9b00683. PubMed DOI PMC
Monticelli L.; Kandasamy S. K.; Periole X.; Larson R. G.; Tieleman D. P.; Marrink S.-J. The MARTINI coarse-grained force field: extension to proteins. J. Chem. Theory Comput. 2008, 4, 819–834. 10.1021/ct700324x. PubMed DOI
de Jong D. H.; Singh G.; Bennett W. D.; Arnarez C.; Wassenaar T. A.; Schäfer L. V.; Periole X.; Tieleman D. P.; Marrink S. J. Improved parameters for the Martini coarse-grained protein force field. J. Chem. Theory Comput. 2013, 9, 687–697. 10.1021/ct300646g. PubMed DOI
Marrink S. J.; Risselada H. J.; Yefimov S.; Tieleman D. P.; De Vries A. H. The MARTINI force field: coarse grained model for biomolecular simulations. J. Phys. Chem. B 2007, 111, 7812–7824. 10.1021/jp071097f. PubMed DOI
Javanainen M.; Martinez-Seara H.; Vattulainen I. Excessive aggregation of membrane proteins in the Martini model. PLoS One 2017, 12, e018793610.1371/journal.pone.0187936. PubMed DOI PMC
Abraham M. J.; Murtola T.; Schulz R.; Páll S.; Smith J. C.; Hess B.; Lindahl E. GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 2015, 1, 19–25. 10.1016/j.softx.2015.06.001. DOI
Javanainen M.Simulations of a membrane with a dilute concentration of proteins in different system sizes. [Data set] 2020; 10.5281/zenodo.3604139. DOI
Javanainen M.; Martinez-Seara H.; Metzler R.; Vattulainen I.. Coarse-grained simulations of lipid membranes with various concentrations of embedded proteins. [Data set] 2017; 10.5281/zenodo.846428. DOI
Javanainen M.Simulations of single-protein membranes. [Data set] 2019; 10.5281/zenodo.3572299. DOI
Javanainen M.Single-protein simulations of different proteins and at various temperatures. [Data set] 2020; 10.5281/zenodo.3604448. DOI
Javanainen M.Single-protein simulations with a varying lipid-to-protein ratio. [Data set] 2020; 10.5281/zenodo.3604384. DOI
Javanainen M.Medium membranes with a single protein at different temperatures. [Data set] 2020; 10.5281/zenodo.3604687. DOI
Javanainen M.Large membranes with a single protein at different temperatures. [Data set] 2020; 10.5281/zenodo.3604731. DOI
Javanainen M.Small membranes crowded with proteins at different temperatures. [Data set] 2020; 10.5281/zenodo.3604282. DOI
Javanainen M.Medium membranes crowded with proteins at different temperatures. [Data set] 2020; 10.5281/zenodo.3604289. DOI
Javanainen M.Large membranes crowded with proteins at different temperatures. [Data set] 2020; 10.5281/zenodo.3604293. DOI
Klauda J. B.; Venable R. M.; Freites J. A.; O’Connor J. W.; Tobias D. J.; Mondragon-Ramirez C.; Vorobyov I.; MacKerell A. D. Jr; Pastor R. W. Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J. Phys. Chem. B 2010, 114, 7830–7843. 10.1021/jp101759q. PubMed DOI PMC
Lim J. B.; Rogaski B.; Klauda J. B. Update of the cholesterol force field parameters in CHARMM. J. Phys. Chem. B 2012, 116, 203–210. 10.1021/jp207925m. PubMed DOI
Jorgensen W. L.; Chandrasekhar J.; Madura J. D.; Impey R. W.; Klein M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983, 79, 926–935. 10.1063/1.445869. DOI
Durell S. R.; Brooks B. R.; Ben-Naim A. Solvent-induced forces between two hydrophilic groups. J. Phys. Chem. 1994, 98, 2198–2202. 10.1021/j100059a038. DOI
Javanainen M.Simulations of different single-component bilayers, three different system sizes. [Data set] 2022; 10.5281/zenodo.6943413. DOI
Javanainen M.Simulations of POPC/cholesterol mixtures at 333 K, three system sizes. [Data set] 2022; 10.5281/zenodo.6943929. DOI
Javanainen M.Simulations of POPC/cholesterol mixtures at 298 K, three system sizes. [Data set] 2021; 10.5281/zenodo.7035350. DOI
Javanainen M.Simulations of a DOPC bilayer at different temperatures, three system sizes. [Data set] 2022; 10.5281/zenodo.6943086. DOI
Ong E. E.; Liow J.-L. The temperature-dependent structure, hydrogen bonding and other related dynamic properties of the standard TIP3P and CHARMM-modified TIP3P water models. Fluid Phase Equilib. 2019, 481, 55–65. 10.1016/j.fluid.2018.10.016. DOI
von Bülow S.; Bullerjahn J. T.; Hummer G. Systematic errors in diffusion coefficients from long-time molecular dynamics simulations at constant pressure. J. Chem. Phys. 2020, 153, 021101.10.1063/5.0008316. PubMed DOI
Bullerjahn J. T.; von Bülow S.; Hummer G. Optimal estimates of self-diffusion coefficients from molecular dynamics simulations. J. Chem. Phys. 2020, 153, 024116.10.1063/5.0008312. PubMed DOI
Palmer B. J. Transverse-current autocorrelation-function calculations of the shear viscosity for molecular liquids. Phys. Rev. E 1994, 49, 359.10.1103/PhysRevE.49.359. PubMed DOI
Bigelow D.; Squier T.; Thomas D. Temperature dependence of rotational dynamics of protein and lipid in sarcoplasmic reticulum membrane. Biochemistry 1986, 25, 194–202. 10.1021/bi00349a028. PubMed DOI
Vaz W. L.; Criado M.; Madeira V. M.; Schoellmann G.; Jovin T. M. Size dependence of the translational diffusion of large integral membrane proteins in liquid-crystalline phase lipid bilayers. A study using fluorescence recovery after photobleaching. Biochemistry 1982, 21, 5608–5612. 10.1021/bi00265a034. PubMed DOI
Marrink S. J.; Tieleman D. P. Perspective on the Martini model. Chem. Soc. Rev. 2013, 42, 6801–6822. 10.1039/c3cs60093a. PubMed DOI
Wu Y.; Štefl M.; Olzyńska A.; Hof M.; Yahioglu G.; Yip P.; Casey D. R.; Ces O.; Humpolíčková J.; Kuimova M. K. Molecular rheometry: direct determination of viscosity in Lo and Ld lipid phases via fluorescence lifetime imaging. Phys. Chem. Chem. Phys. 2013, 15, 14986–14993. 10.1039/c3cp51953h. PubMed DOI
Filippov A.; Orädd G.; Lindblom G. The effect of cholesterol on the lateral diffusion of phospholipids in oriented bilayers. Biophys. J. 2003, 84, 3079–3086. 10.1016/S0006-3495(03)70033-2. PubMed DOI PMC
Filippov A.; Orädd G.; Lindblom G. Influence of cholesterol and water content on phospholipid lateral diffusion in bilayers. Langmuir 2003, 19, 6397–6400. 10.1021/la034222x. DOI
Chwastek G.; Petrov E. P.; Sáenz J. P. A method for high-throughput measurements of viscosity in sub-micrometer-sized membrane systems. ChemBioChem. 2020, 21, 836.10.1002/cbic.201900510. PubMed DOI PMC
Merkel R.; Sackmann E.; Evans E. Molecular friction and epitactic coupling between monolayers in supported bilayers. J. Phys. (Paris) 1989, 50, 1535–1555. 10.1051/jphys:0198900500120153500. DOI
Amador G. J.; van Dijk D.; Kieffer R.; Aubin-Tam M.-E.; Tam D. Hydrodynamic shear dissipation and transmission in lipid bilayers. Proc. Natl. Acad. Sci. U.S.A. 2021, 118, e2100156118.10.1073/pnas.2100156118. PubMed DOI PMC
Fitzgerald J. E.; Venable R. M.; Pastor R. W.; Lyman E. R. Surface viscosities of lipid bilayers determined from equilibrium molecular dynamics simulations. Biophys. J. 2023, 122, 227a.10.1016/j.bpj.2022.11.1345. PubMed DOI PMC
Róg T.; Pasenkiewicz-Gierula M.; Vattulainen I.; Karttunen M. Ordering effects of cholesterol and its analogues. Biochim. Biophys. Acta 2009, 1788, 97–121. 10.1016/j.bbamem.2008.08.022. PubMed DOI
Schachter I.; Paananen R. O.; Fabian B.; Jurkiewicz P.; Javanainen M. The Two Faces of Liquid Ordered Phase. J. Phys. Chem. Lett. 2022, 13, 1307–1313. 10.1021/acs.jpclett.1c03712. PubMed DOI PMC
Falck E.; Patra M.; Karttunen M.; Hyvönen M. T.; Vattulainen I. Lessons of slicing membranes: interplay of packing, free area, and lateral diffusion in phospholipid/cholesterol bilayers. Biophys. J. 2004, 87, 1076–1091. 10.1529/biophysj.104.041368. PubMed DOI PMC
Hofsäß C.; Lindahl E.; Edholm O. Molecular dynamics simulations of phospholipid bilayers with cholesterol. Biophys. J. 2003, 84, 2192–2206. 10.1016/S0006-3495(03)75025-5. PubMed DOI PMC
Greenwood A. I.; Tristram-Nagle S.; Nagle J. F. Partial molecular volumes of lipids and cholesterol. Chem. Phys. Lipids 2006, 143, 1–10. 10.1016/j.chemphyslip.2006.04.002. PubMed DOI PMC
Zhuang X.; Makover J. R.; Im W.; Klauda J. B. A systematic molecular dynamics simulation study of temperature dependent bilayer structural properties. Biochim. Biophys. Acta 2014, 1838, 2520–2529. 10.1016/j.bbamem.2014.06.010. PubMed DOI
Zhuang X.; Dávila-Contreras E. M.; Beaven A. H.; Im W.; Klauda J. B. An extensive simulation study of lipid bilayer properties with different head groups, acyl chain lengths, and chain saturations. Biochim. Biophys. Acta 2016, 1858, 3093–3104. 10.1016/j.bbamem.2016.09.016. PubMed DOI