Cholesterol translocation in a phospholipid membrane

Amit Choubey; Rajiv K Kalia; Noah Malmstadt; Aiichiro Nakano; Priya Vashishta

doi:10.1016/j.bpj.2013.04.036

Cholesterol translocation in a phospholipid membrane

Biophys J. 2013 Jun 4;104(11):2429-36. doi: 10.1016/j.bpj.2013.04.036.

Authors

Amit Choubey¹, Rajiv K Kalia, Noah Malmstadt, Aiichiro Nakano, Priya Vashishta

Affiliation

¹ Department of Physics and Astronomy, University of Southern California, Los Angeles, CA, USA.

Abstract

Cholesterol (CHOL) molecules play a key role in modulating the rigidity of cell membranes and controlling intracellular transport and signal transduction. Using an all-atom molecular dynamics approach, we study the process of CHOL interleaflet transport (flip-flop) in a dipalmitoylphosphatidycholine (DPPC)-CHOL bilayer over a time period of 15 μs. We investigate the effect of the flip-flop process on mechanical stress across the bilayer and the role of CHOL in inducing molecular order in bilayer leaflets. The simulations are carried out at physiologically relevant CHOL concentration (30%), temperature (323 K), and pressure (1 bar). CHOL flip-flop events are observed with a rate constant of 3 × 10⁴s⁻¹. Once a flip-flop event is triggered, a CHOL molecule takes an average of 73 nanoseconds to migrate from one bilayer leaflet to the other.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

1,2-Dipalmitoylphosphatidylcholine / chemistry
1,2-Dipalmitoylphosphatidylcholine / metabolism*
Biological Transport
Cell Membrane / chemistry
Cell Membrane / metabolism*
Cholesterol / chemistry
Cholesterol / metabolism*
Molecular Conformation
Molecular Dynamics Simulation*
Pressure

Substances

1,2-Dipalmitoylphosphatidylcholine
Cholesterol