General anesthesia can be caused by various, chemically very different molecules, while several other molecules, many of which are structurally rather similar to them, do not exhibit anesthetic effects at all. To understand the origin of this difference and shed some light on the molecular mechanism of general anesthesia, we report here molecular dynamics simulations of the neat dipalmitoylphosphatidylcholine (DPPC) membrane as well as DPPC membranes containing the anesthetics diethyl ether and chloroform and the structurally similar non-anesthetics n-pentane and carbon tetrachloride, respectively. To also account for the pressure reversal of anesthesia, these simulations are performed both at 1 bar and at 600 bar. Our results indicate that all solutes considered prefer to stay both in the middle of the membrane and close to the boundary of the hydrocarbon domain, at the vicinity of the crowded region of the polar headgroups. However, this latter preference is considerably stronger for the (weakly polar) anesthetics than for the (apolar) non-anesthetics. Anesthetics staying in this outer preferred position increase the lateral separation between the lipid molecules, giving rise to a decrease of the lateral density. The lower lateral density leads to an increased mobility of the DPPC molecules, a decreased order of their tails, an increase of the free volume around this outer preferred position, and a decrease of the lateral pressure at the hydrocarbon side of the apolar/polar interface, a change that might well be in a causal relation with the occurrence of the anesthetic effect. All these changes are clearly reverted by the increase of pressure. Furthermore, non-anesthetics occur in this outer preferred position in a considerably smaller concentration and hence either induce such changes in a much weaker form or do not induce them at all.

Department of Chemistry Eszterházy Károly Catholic University Leányka utca 6 H 3300 Eger Hungary

Institute of Chemistry University of Miskolc Egyetemváros A 2 H 3515 Miskolc Hungary

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo náměstí 2 CZ 16610 Prague 6 Czech Republic

Institute of Physics and Materials Science University of Natural Resources and Life Sciences Peter Jordan Straße 82 A 1190 Vienna Austria

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Meyer H. Zur Theorie der Alkoholnarkose. N. Schmied. Arch. Pharmacol. 1899, 42, 109–118. 10.1007/bf01834479. DOI

Overton E.Studien über die Narkose zugleich ein Beitrag zur allgemeinen Pharmakologei; Gustav Fischer Verlag: Jena, 1901.

Franks N. P.; Lieb W. R. Where Do General Anesthetics Act?. Nature 1978, 274, 339–342. 10.1038/274339a0. PubMed DOI

Franks N. P.; Lieb W. R. Molecular and cellular mechanisms of general anaesthesia. Nature 1994, 367, 607–614. 10.1038/367607a0. PubMed DOI

Mitchell D. C.; Lawrence J. T. R.; Litman B. J. Primary Alcohols Modulate the Activation of the G Protein-Coupled Receptor Rhodopsin by a Lipid-Mediated Mechanism. J. Biol. Chem. 1996, 271, 19033–19036. 10.1074/jbc.271.32.19033. PubMed DOI

Mihic S. J.; Ye Q.; Wick M. J.; Koltchine V. V.; Krasowski M. D.; Finn S. E.; Mascia M. P.; Valenzuela C. F.; Hanson K. K.; Greenblatt E. P.; et al. Sites of Alcohol and Volatile Anesthetic Action on GABAA and Glycine Receptors. Nature 1997, 389, 385–389. 10.1038/38738. PubMed DOI

Mohr J. T.; Gribble G. W.; Lin S. S.; Eckenhoff R. G.; Cantor R. S. Anesthetic Potency of Two Novel Synthetic Polyhydric Alkanols Longer than the n-Alkanol Cutoff: Evidence for a Bilayer-Mediated Mechanism of Anesthesia?. J. Med. Chem. 2005, 48, 4172–4176. 10.1021/jm049459k. PubMed DOI

Cantor R. S. Breaking the Meyer-Overton Rule: Predicted Effects of Varying Stiffness and Interfacial Activity on the Intrinsic Potency of Anesthetics. Biophys. J. 2001, 80, 2284–2297. 10.1016/s0006-3495(01)76200-5. PubMed DOI PMC

Græsbøll K.; Sasse-Middelhoff H.; Heimburg T. The Thermodynamics of General and Local Anesthesia. Biophys. J. 2014, 106, 2143–2156. 10.1016/j.bpj.2014.04.014. PubMed DOI PMC

Kelz M. B.; Mashour G. A. The Biology of General Anesthesia from Paramecium to Primate. Curr. Biol. 2019, 29, R1199–R1210. 10.1016/j.cub.2019.09.071. PubMed DOI PMC

Johnson F. H.; Flagler E. A. Hydrostatic Pressure Reversal of Narcosis in Tadpoles. Science 1950, 112, 91–92. 10.1126/science.112.2899.91-a. PubMed DOI

Johnson S. M.; Miller K. W. Antagonism of Pressure and Anaesthesia. Nature 1970, 228, 75–76. 10.1038/228075b0. PubMed DOI

Lever M. J.; Miller K. W.; Paton W. D. M.; Smith E. B. Pressure Reversal of Anaesthesia. Nature 1971, 231, 368–371. 10.1038/231368a0. PubMed DOI

Halsey M. J.; Wardley-Smith B. Pressure Reversal of Narcosis Produced by Anesthetics, Narcotics and Tranquillisers. Nature 1975, 257, 811–813. PubMed

Trudell J. R.; Payan D. G.; Chin J. H.; Cohen E. N. The Antagonistic Effect of an Inhalation Anesthetic and High Pressure on the Phase Diagram of Mixed Dipalmitoyl-Dimyristoylphosphatidylcholine Bilayers. Proc. Natl. Acad. Sci. U.S.A. 1975, 72, 210–213. 10.1073/pnas.72.1.210. PubMed DOI PMC

Mullins L. J. Some Physical Mechanisms in Narcosis. Chem. Rev. 1954, 54, 289–323. 10.1021/cr60168a003. DOI

Booker R. D.; Sum A. K. Biophysical Changes Induced by Xenon on Phospholipid Bilayers. Biochim. Biophys. Acta 2013, 1828, 1347–1356. 10.1016/j.bbamem.2013.01.016. PubMed DOI

Moskovitz Y.; Yang H. Modelling of noble anaesthetic gases and high hydrostatic pressure effects in lipid bilayers. Soft Matter 2015, 11, 2125–2138. 10.1039/c4sm02667e. PubMed DOI

Haydon D. A.; Hendry B. M.; Levinson S. R.; Requena J. The molecular mechanisms of anaesthesia. Nature 1977, 268, 356–358. 10.1038/268356a0. PubMed DOI

Trudell J. R.; Hubbell W. L.; Cohen E. N. The effect of two inhalation anesthetics of the order of spin-labeled phospholipid vesicles. Biochim. Biophys. Acta 1973, 291, 321–327. 10.1016/0005-2736(73)90485-9. PubMed DOI

Franks N. P.; Lieb W. R. The structure of lipid bilayers and the effects of general anaesthetics. J. Mol. Biol. 1979, 133, 469–500. 10.1016/0022-2836(79)90403-0. PubMed DOI

Tu K.; Tarek M.; Klein M. L.; Scharf D. Effects of Anesthetics on the Structure of a Phospholipid Bilayer: Molecular Dynamics Investigation of Halothane in the Hydrated Liquid Crystal Phase of Dipalmitoylphosphatidylcholine. Biophys. J. 1998, 75, 2123–2134. 10.1016/s0006-3495(98)77655-6. PubMed DOI PMC

Koubi L.; Tarek M.; Klein M. L.; Scharf D. Distribution of Halothane in a Dipalmitoylphosphatidylcholine Bilayer from Molecular Dynamics Calculations. Biophys. J. 2000, 78, 800–811. 10.1016/s0006-3495(00)76637-9. PubMed DOI PMC

Lee B. W.; Faller R.; Sum A. K.; Vattulainen I.; Patra M.; Karttunen M. Structural effects of small molecules on phospholipid bilayers investigated by molecular simulations. Fluid Phase Equilib. 2005, 228–229, 135–140. 10.1016/j.fluid.2005.03.002. DOI

Patra M.; Salonen E.; Terama E.; Vattulainen I.; Faller R.; Lee B. W.; Holopainen J.; Karttunen M. Under the Influence of Alcohol: The Effect of Ethanol and Methanol on Lipid Bilayers. Biophys. J. 2006, 90, 1121–1135. 10.1529/biophysj.105.062364. PubMed DOI PMC

Frischknecht A. L.; Frink L. J. D. Alcohols Reduce Lateral Membrane Pressures: Predictions from Molecular Theory. Biophys. J. 2006, 91, 4081–4090. 10.1529/biophysj.106.091918. PubMed DOI PMC

Griepernau B.; Böckmann R. A. The Influence of 1-Alkanols and External Pressure on the Lateral Pressure Profiles of Lipid Bilayers. Biophys. J. 2008, 95, 5766–5778. 10.1529/biophysj.108.142125. PubMed DOI PMC

Gurtovenko A. A.; Anwar J. Interaction of Ethanol with Biological Membranes: The Formation of Non-bilayer Structures within the Membrane Interior and their Significance. J. Phys. Chem. B 2009, 113, 1983–1992. 10.1021/jp808041z. PubMed DOI

Oh K.-J.; Klein M. L. Effects of Halothane on Dimyristoylphosphatidylcholine Lipid Bilayer Structure: A Molecular Dynamics Simulation Study. Bull. Korean Chem. Soc. 2009, 30, 2087–2092. 10.5012/bkcs.2009.30.9.2087. DOI

Jerabek H.; Pabst G.; Rappolt M.; Stockner T. Membrane-Mediated Effect on Ion Channels Induced by the Anesthetic Drug Ketmine. J. Am. Chem. Soc. 2010, 132, 7990–7997. 10.1021/ja910843d. PubMed DOI

Darvas M.; Hoang P. N. M.; Picaud S.; Sega M.; Jedlovszky P. Anesthetic Molecules Embedded in a Lipid Membrane: A Computer Simulation Study. Phys. Chem. Chem. Phys. 2012, 14, 12956–12969. 10.1039/c2cp41581j. PubMed DOI

Fábián B.; Darvas M.; Picaud S.; Sega M.; Jedlovszky P. The effect of anaesthetics on the properties of a lipid membrane in the biologically relevant phase: a computer simulation study. Phys. Chem. Chem. Phys. 2015, 17, 14750–14760. 10.1039/c5cp00851d. PubMed DOI

Hantal G.; Fábián B.; Sega M.; Jójárt B.; Jedlovszky P. Effect of General Anesthetics on the Properties of Lipid Membranes of Various Compositions. Biochim. Biophys. Acta Biomembr. 2019, 1861, 594–609. 10.1016/j.bbamem.2018.12.008. PubMed DOI

Jedlovszky P.Simulation of Membranes Containing General Anesthetics. In Biomembrane Simulations. Computational Studies of Biological Membranes; Berkowitz M. L., Ed.; Taylor and Francis: New York, 2019; pp 177–198. and references therein.

Ly H. V.; Block D. E.; Longo M. L. Interfacial Tension Effect of Ethanol on Lipid Bilayer Rigidity, Stability, and Area/Molecule: A Micropipet Aspiration Approach. Langmuir 2002, 18, 8988–8995. 10.1021/la026010q. DOI

Ly H. V.; Longo M. L. The Influence of Short-Chain Alcohols on Interfacial Tension, Mechanical Properties, Area/Molecule, and Permeability of Fluid Lipid Bilayers. Biophys. J. 2004, 87, 1013–1033. 10.1529/biophysj.103.034280. PubMed DOI PMC

Stimson L. M.; Vattulainen I.; Róg T.; Karttunen M. Exploring the Effect of Xenon on Biomembranes. Cell. Mol. Biol. Lett. 2005, 10, 563–569. PubMed

Griepernau B.; Leis S.; Schneider M. F.; Sikor M.; Steppich D.; Böckmann R. A. 1-Alkanols and Membranes: A Story of Attraction. Biochim. Biophys. Acta 2007, 1768, 2899–2913. 10.1016/j.bbamem.2007.08.002. PubMed DOI

Dickey A. N.; Faller R. How Alcohol Chain-Length and Concentration Modulate Hydrogen Bond Formation in a Lipid Bilayer. Biophys. J. 2007, 92, 2366–2376. 10.1529/biophysj.106.097022. PubMed DOI PMC

Reigada R. Influence of Chloroform in Liquid-Ordered and Liquid-Disordered Phases in Lipid Membranes. J. Phys. Chem. B 2011, 115, 2527–2535. 10.1021/jp110699h. PubMed DOI

Yamamoto E.; Akimoto T.; Shimizu H.; Hirano Y.; Yasui M.; Yasuoka K. Diffusive Nature of Xenon Anesthetic Changes Properties of a Lipid Bilayer: Molecular Dynamics Simulations. J. Phys. Chem. B 2012, 116, 8989–8995. 10.1021/jp303330c. PubMed DOI

Reigada R. Atomistic Study of Lipid Membranes Containing Chloroform: Looking for a Lipid-Mediated Mechanism of Anesthesia. PLoS One 2013, 8, e5263110.1371/journal.pone.0052631. PubMed DOI PMC

Chen J.; Chen L.; Wang Y.; Wang X.; Zeng S. Exploring the Effects on Lipid Bilayer Induced by Noble Gases via Molecular Dynamics Simulations. Sci. Rep. 2015, 5, 17235.10.1038/srep17235. PubMed DOI PMC

Janoff A. S.; Miller K. W.. Biological Membranes; Chapman D., Ed.; Academic Press: London, 1982; pp 417–476.

Forrest B. J.; Rodham D. K. An anaesthetic-induced phosphatidylcholine hexagonal phase. Biochim. Biophys. Acta 1985, 814, 281–288. 10.1016/0005-2736(85)90446-8. DOI

Kaminoh Y.; Tashiro C.; Kamaya H.; Ueda I. Depression of Phase-Transition Temperature by Anesthetics: Nonzero Solid Membrane Binding. Biochim. Biophys. Acta 1988, 946, 215–220. 10.1016/0005-2736(88)90395-1. PubMed DOI

Kaminoh Y.; Nishimura S.; Kamaya H.; Ueda I. Alcohol Interaction with High Entropy States of Macromolecules: Critical Temperature Hypothesisfor Anesthesia Cutoff. Biochim. Biophys. Acta 1992, 1106, 335–343. 10.1016/0005-2736(92)90014-d. PubMed DOI

Heimburg T.; Jackson A. D. The Thermodynamics of General Anesthesia. Biophys. J. 2007, 92, 3159–3165. 10.1529/biophysj.106.099754. PubMed DOI PMC

Sierra-Valdez F. J.; Ruiz-Suárez J. C. Noble Gases in Pure Lipid Membranes. J. Phys. Chem. B 2013, 117, 3167–3172. 10.1021/jp400367t. PubMed DOI

Chanda J.; Bandyopadhyay S. Distribution of Ethanol in a Model Membrane: A Computer Simulation Study. Chem. Phys. Lett. 2004, 392, 249–254. 10.1016/j.cplett.2004.05.072. DOI

Pickholz M.; Saiz L.; Klein M. L. Concentration Effects of Volatile Anesthetics on the Properties of Model Membranes: A Coarse-Grain Approach. Biophys. J. 2005, 88, 1524–1534. 10.1529/biophysj.104.044354. PubMed DOI PMC

Chanda J.; Bandyopadhyay S. Perturbation of Phospholipid Bilayer Properties by Ethanol at a High Concentration. Langmuir 2006, 22, 3775–3781. 10.1021/la053398r. PubMed DOI

Terama E.; Ollila O. H. S.; Salonen E.; Rowat A. C.; Trandum C.; Westh P.; Patra M.; Karttunen M.; Vattulainen I. Influence of Ethanol on Lipid Membranes: From Lateral Pressure Profiles to Dynamics and Partitioning. J. Phys. Chem. B 2008, 112, 4131–4139. 10.1021/jp0750811. PubMed DOI

Cantor R. S. Lateral Pressures in Cell Membranes: A Mechanism for Modulation of Protein Function. J. Phys. Chem. B 1997, 101, 1723–1725. 10.1021/jp963911x. DOI

Cantor R. S. The Lateral Pressure Profile in Membranes: A Physical Mechanism of General Anesthesia. Biochemistry 1997, 36, 2339–2344. 10.1021/bi9627323. PubMed DOI

Schofield P.; Henderson J. R. Statistical Mechanics of Inhomogeneous Fluids. Proc. R. Soc. London, Ser. A 1982, 379, 231–246. 10.1098/rspa.1982.0015. DOI

Sonne J.; Hansen F. Y.; Peters G. H. Methodological Problems in Pressure Profile Calculations for Lipid Bilayers. J. Chem. Phys. 2005, 122, 124903.10.1063/1.1862624. PubMed DOI

Sega M.; Fábián B.; Jedlovszky P. Pressure Profile Calculation with Mesh Ewald Methods. J. Chem. Theory Comput. 2016, 12, 4509–4515. 10.1021/acs.jctc.6b00576. PubMed DOI

Fábián B.; Sega M.; Voloshin V. P.; Medvedev N. N.; Jedlovszky P. Lateral Pressure Profile and Free Volume Properties in Phospholipid Membranes Containing Anesthetics. J. Phys. Chem. B 2017, 121, 2814–2824. 10.1021/acs.jpcb.7b00990. PubMed DOI

Hauet N. F.; Artzner F.; Boucher F.; Grabielle-Madelmont C.; Cloutier I.; Keller G.; Lesieur P.; Durand D.; Paternostre M. Interaction between Artificial Membranes and Enflurane, a General Volatile Anesthetic: DPPC-Enflurane Interaction. Biophys. J. 2003, 84, 3123–3137. 10.1016/s0006-3495(03)70037-x. PubMed DOI PMC

Jin L.; Laster M. J.; Taheri S.; Eger E. I. II; Koblin D. D.; Halsey M. J. Is There a Cutoff in Anesthetic Potency for the Normal Alkanes?. Anesth. Analg. 1993, 77, 12–18. 10.1213/00000539-199307000-00004. PubMed DOI

Zhang Y.; Eger E. I. II; Dutton R. C.; Sonner J. M. Inhaled Anesthetics Have Hyperalgesic Effects at 0.1 Minimum Alveloar Anesthetic Concentration. Anesth. Analg. 2000, 91, 462–466. 10.1097/00000539-200008000-00044. PubMed DOI

Nagle J. F.; Zhang R.; Tristram-Nagle S.; Sun W.; Petrache H. I.; Suter R. M. X-Ray Structure Determination of Fully Hydrated Lα Phase Dipalmitoylphosphatidylcholine Bilayers. Biophys. J. 1996, 70, 1419–1431. 10.1016/s0006-3495(96)79701-1. PubMed DOI PMC

Klauda J. B.; Venable R. M.; Freites J. A.; O’Connor J. W.; Tobias D. J.; Mondragon-Ramirez C.; Vorobyov I.; MacKerell A. D.; 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

Zoete V.; Cuendet M. A.; Grosdidier A.; Michielin O. SwissParam, a Fast Force Field Generation Tool For Small Organic Molecules. J. Comput. Chem. 2011, 32, 2359–2368. 10.1002/jcc.21816. PubMed DOI

SIB . SwissParam. https://www.swissparam.ch (accessed Feb 23, 2023).

Neria E.; Fischer S.; Karplus M. Simulation of Activation Free Energies in Molecular Systems. J. Chem. Phys. 1996, 105, 1902–1921. 10.1063/1.472061. DOI

Miyamoto S.; Kollman P. A. Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models. J. Comput. Chem. 1992, 13, 952–962. 10.1002/jcc.540130805. DOI

Hess B. P-LINCS: A Parallel Linear Constraint Solver for Molecular Simulation. J. Chem. Theory Comput. 2008, 4, 116–122. 10.1021/ct700200b. PubMed DOI

Essmann U.; Perera L.; Berkowitz M. L.; Darden T.; Lee H.; Pedersen L. G. A Smooth Particle Mesh Ewald Method. J. Chem. Phys. 1995, 103, 8577–8593. 10.1063/1.470117. DOI

Pronk S.; Páll S.; Schulz R.; Larsson P.; Bjelkmar P.; Apostolov R.; Shirts M. R.; Smith J. C.; Kasson P. M.; van der Spoel D.; et al. GROMACS 4.5: A High-Throughput and Highly Parallel Open Source Molecular Simulation Toolkit. Bioinformatics 2013, 29, 845–854. 10.1093/bioinformatics/btt055. PubMed DOI PMC

GitHub . Marcello-Sega/gromacs. The code is freely available at https://github.com/Marcello-Sega/gromacs/tree/virial/ (accessed Jan 27, 2023).

Allen M. P.; Tildesley D. J.. Computer Simulation of Liquids; Clarendon Press: Oxford, 1987.

Nosé S. A Molecular Dynamics Method for Simulations in the Canonical Ensemble. Mol. Phys. 1984, 52, 255–268. 10.1080/00268978400101201. DOI

Hoover W. G. Canonical Dynamics: Equilibrium Phase-Space Distributions. Phys. Rev. A 1985, 31, 1695–1697. 10.1103/physreva.31.1695. PubMed DOI

Parrinello M.; Rahman A. Polymorphic Transitions in Single Crystals: A New Molecular Dynamics Method. J. Appl. Phys. 1981, 52, 7182–7190. 10.1063/1.328693. DOI

Harasima A.Molecular Theory of Surface Tension. Advances in Chemical Physics; Wiley, 1958; Vol. 1, pp 203–237.

Ewald P. Die Berechnung Optischer und Elektrostatischer Gitterpotentiale. Ann. Phys. 1921, 369, 253–287. 10.1002/andp.19213690304. DOI

de Leeuw S. W.; Perram J. W.; Smith E. R. Simulation of Electrostatic Systems in Periodic Boundary Conditions. I. Lattice Sums and Dielectric Constants. Proc. R. Soc. London, Ser. A 1980, 373, 27–56. 10.1098/rspa.1980.0135. DOI

Darden T.; York D.; Pedersen L. Particle Mesh Ewald: An N·log(N) Method for Ewald Sums in Large Systems. J. Chem. Phys. 1993, 98, 10089–10092. 10.1063/1.464397. DOI

Sega M.; Fábián B.; Jedlovszky P. Layer-by-Layer and Intrinsic Analysis of Molecular and Thermodynamic Properties Across Soft Interfaces. J. Chem. Phys. 2015, 143, 114709.10.1063/1.4931180. PubMed DOI

Rózsa Z. B.; Fábián B.; Hantal G.; Szőri M.; Jedlovszky P. Effect of Xenon, an Apolar General Anaesthetic on the Properties of the DPPC Bilayer. J. Mol. Liq. 2023, 12240510.1016/j.molliq.2023.122405. DOI

Nagle J. F. Area/Lipid of Bilayers from NMR. Biophys. J. 1993, 64, 1476–1481. 10.1016/s0006-3495(93)81514-5. PubMed DOI PMC

Wiener M. C.; Tristram-Nagle S.; Wilkinson D. A.; Campbell L. E.; Nagle J. F. Specific Volumes of Lipids in Fully Hydrated Bilayer Dispersions. Biochim. Biophys. Acta Biomembr. 1988, 938, 135–142. 10.1016/0005-2736(88)90153-8. PubMed DOI

López-Cascales J. J.; García de la Torre J.; Marrink S. J.; Berendsen H. J. C. Molecular dynamics simulation of a charged biological membrane. J. Chem. Phys. 1996, 104, 2713–2720. 10.1063/1.470992. DOI

Mezei M.; Jedlovszky P.. Statistical Thermodynamics via Computer Simulation to Characterize Phospholipid Interactions in Membranes. In Methods in Molecular Biology; Dopico A. M., Ed.; Methods in Membrane Lipid; Humana Press: Totowa, NJ, 2007; Vol. 400, pp 127–144. PubMed

Douliez J. P.; Léonard A.; Dufourc E. J. Restatement of Order Parameters in Biomembranes: Calculation of C-C Bond Order Parameters from C-D Quadrupolar Splittings. Biophys. J. 1995, 68, 1727–1739. 10.1016/s0006-3495(95)80350-4. 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

Orädd G.; Westerman P. W.; Lindblom G. Lateral Diffusion Coefficients of Separate Lipid Species in a Ternary Raft-Forming Bilayer: A Pfg-NMR Multinuclear Study. Biophys. J. 2005, 89, 315–320. 10.1529/biophysj.105.061762. PubMed DOI PMC

Sega M.; Fábián B.; Horvai G.; Jedlovszky P. How Is the Surface Tension of Various Liquids Distributed along the Interface Normal?. J. Phys. Chem. C 2016, 120, 27468–27477. 10.1021/acs.jpcc.6b09880. DOI

Pavel M. A.; Petersen E. N.; Wang H.; Lerner R. A.; Hansen S. B. Studies on the Mechanism of General Anesthesia. Proc. Natl. Acad. Sci. U.S.A. 2020, 117, 13757–13766. 10.1073/pnas.2004259117. PubMed DOI PMC