title: Flip-flop of oleic acid in a phospholipid membrane: rate and mechanism.
abstract: Flip-flop of protonated oleic acid molecules dissolved at two different concentrations in membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine is studied with the aid of molecular dynamics simulations at a time scale of several microseconds. Direct, single-molecule flip-flop events are observed at this time scale, and the flip-flop rate is estimated at 0.2-0.3 μs(-1). As oleic acid molecules move toward the center of the bilayer during flip-flop, they undergo gradual, correlated translational, and rotational motion. Rare, double-flipping events of two hydrogen-bonded oleic acid molecules are also observed. A two-dimensional free energy surface is obtained for the translational and rotational degree of freedom of the oleic acid molecule, and the minimum energy path on this surface is determined. A barrier to flip-flop of ~4.2 kcal/mol is found at the center of the bilayer. A two-dimensional diffusion model is found to provide a good description of the flip-flop process. The fast flip-flop rate lends support to the proposal that fatty acids permeate membranes without assistance of transport proteins. It also suggests that desorption rather than flip-flop is the rate-limiting step in fatty acid transport through membranes. The relation of flip-flop rates to the evolution of ancestral cellular systems is discussed.
authors.affiliation: NASA Ames Research Center , Mail Stop 229-1, Moffett Field, California 94035, United States.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Wei
authors.forename: Andrew
authors.initials: A
authors.lastname: Pohorille
mesh_terms: D004058:Diffusion; D008051:Lipid Bilayers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D019301:Oleic Acid / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010743:Phospholipids; D019301:Oleic Acid; C028694:1-palmitoyl-2-oleoylphosphatidylcholine