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Updated: Jul 10, 2026
09:52
A Fluorescence-based Assay of Phospholipid Scramblase Activity
Published on: September 20, 2016
Molecular mechanism for lipid flip-flops
Andrey A Gurtovenko1, Ilpo Vattulainen
1Computational Laboratory, Institute of Pharmaceutical Innovation, University of Bradford, Bradford, West Yorkshire, BD7 1DP, United Kingdom. A.Gurtovenko@bradford.ac.uk
The Journal of Physical Chemistry. B
|November 9, 2007
Summary
Transmembrane lipid translocation (flip-flop) occurs spontaneously in cell membranes via transient water pores. Membrane defects, not pore formation method, drive lipid flip-flops, explaining experimental observations.
Area of Science:
- Biophysics
- Cell Biology
- Membrane Dynamics
Background:
- Transmembrane lipid translocation (flip-flop) is crucial for membrane asymmetry and cell death.
- Flip-flop mechanisms remain poorly understood despite their importance.
Purpose of the Study:
- To elucidate the molecular mechanism of pore-mediated transmembrane lipid translocation.
- To investigate spontaneous lipid flip-flops in protein-free membranes.
Main Methods:
- Extensive atomistic molecular dynamics simulations.
- Analysis of 50 resolved lipid flip-flop events.
Main Results:
- Lipid flip-flops occur spontaneously via transient water pores in protein-free membranes under physiological conditions.
- Pore formation, induced by ion gradients or other means, leads to diffusive lipid translocation driven by thermal fluctuations.
- Water pore formation is the rate-limiting step for transmembrane lipid flip-flop, occurring over hours.
Conclusions:
- Pore-mediated lipid translocation is a fundamental process in cell membranes.
- Findings align with experimental data and explain phenomena like electric field pulse effects.
- Provides a molecular basis for interpreting experimental observations on lipid flip-flops.
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