Lipids Out of Equilibrium: Energetics of Desorption and Pore Mediated Flip-Flop

Tieleman, D. Peter; Marrink, Siewert-Jan

doi:10.1021/ja0624321

Cited by 235Lipid Membrane Structure and BehaviorAdvanced Physical and Chemical Molecular InteractionsProtein Structure and Dynamics

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Lipids Out of Equilibrium: Energetics of Desorption and Pore Mediated Flip-Flop

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Tieleman, D. Peter, Marrink, Siewert-Jan·2006·Journal of the American Chemical Society

DOI 10.1021/ja0624321

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Abstract

The potential of mean force (PMF) of a phospholipid in a bilayer is a key thermodynamic property that describes the energetic cost of localized lipid defects. We have calculated the PMF by umbrella sampling using molecular dynamics simulations. The profile has a deep minimum at the equilibrium position in the bilayer and steeply rises for displacements both deeper into the bilayer and moving away from the bilayer. As the lipid loses contact with the bilayer, the profile abruptly flattens without a significant barrier. The calculated free energy difference of 80 kJ/mol between the minimum of the PMF and the value in water agrees well with the free energy difference calculated from the experimentally measured critical micelle concentration. Significant water/lipid defects form when a lipid is forced into the bilayer interior, in the form of a small water pore that spans the membrane. The energy required to form such a water pore is also found to be 80 kJ/mol. On the basis of this energy, we estimate the lipid flip-flop rate and permeability rate of sodium ions. The resulting rates are in good agreement with experimental measurements, suggesting lipid flip-flop and basal permeability of ions are pore mediated.

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Molecular dynamics studies provide detailed information on bilayer entry and exit of individual lipid molecules, including inference on thermodynamic and kinetic parameters.
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Authors: Tieleman, D. P., & Marrink, S.-J.
Affiliations: University of Calgary (CA)
ORCID: Tieleman, D. Peter
Marrink, Siewert-Jan
Venue: Journal of the American Chemical Society
Publisher: American Chemical Society (ACS)
Published: 2006-08-31
Volume: 128
Issue: 38
Pages: 12462-12467
ISSN: 0002-7863 (ISSN-L)
1520-5126
DOI: 10.1021/ja0624321
OpenAlex: W2121138440
Cited by: 230
References: 42
Citations by year: 2026: 13 · 2025: 9 · 2024: 3 · 2023: 9 · 2022: 1 · 2021: 9 · 2020: 8 · 2019: 16 · 2018: 12 · 2017: 15 · 2016: 16 · 2015: 11 · 2014: 20 · 2013: 9 · 2012: 13
FWCI: 6.08
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
Locations: Journal of the American Chemical Society (publishedVersion)
PubMed (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
Funders: Alfred P. Sloan Foundation
Western Canada Research Grid
Fondation pour la Recherche Médicale
Canadian Institutes of Health Research
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Advanced Physical and Chemical Molecular Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords: lipid flip-flop, potential of mean force, phospholipid bilayers, water pores, membrane permeability, sodium ion permeation, critical micelle concentration, activation barrier, membrane defects, umbrella sampling
MeSH terms: Computer Simulation, Kinetics, Lipid Bilayers, Models, Molecular, Phospholipids, Sodium, Water, 1,2-Dipalmitoylphosphatidylcholine

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Lipids Out of Equilibrium: Energetics of Desorption and Pore Mediated Flip-Flop

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