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Cholesterol Flip-Flop in Heterogeneous Membranes.
Ruo-Xu Gu1, Svetlana Baoukina1, D Peter Tieleman1
1Centre for Molecular Simulation and Department of Biological Sciences , University of Calgary , 2500 University Drive, N.W. , Calgary , Alberta T2N 1N4 , Canada.
Journal of Chemical Theory and Computation
|January 12, 2019
Summary
Cholesterol
Area of Science:
- Biochemistry
- Biophysics
- Cell Biology
Background:
- Cholesterol is abundant in mammalian plasma membranes.
- Its distribution between membrane leaflets is vital for cell function.
- Cholesterol flip-flop (trans-bilayer motion) influences this distribution.
Purpose of the Study:
- To investigate cholesterol flip-flop rates.
- To determine the impact of membrane lateral heterogeneity on flip-flop rates.
Main Methods:
- Atomistic molecular dynamics simulations.
- Simulated spontaneous cholesterol flip-flop events in a mixed lipid system (DPPC:DOPC:cholesterol).
Main Results:
- Determined an overall cholesterol flip-flop rate on the sub-millisecond timescale.
- Identified that the local lipid environment significantly affects the cholesterol flip-flop rate.
- Observed and analyzed atomistic details of cholesterol flip-flop events.
Conclusions:
- Cholesterol flip-flop is a dynamic process influenced by membrane composition.
- Local lipid environments play a crucial role in regulating cholesterol trans-bilayer motion.
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