title: Roles of Interleaflet Coupling and Hydrophobic Mismatch in Lipid Membrane Phase-Separation Kinetics.
abstract: Characterizing the nanoscale dynamic organization within lipid bilayer membranes is central to our understanding of cell membranes at a molecular level. We investigate phase separation and communication across leaflets in ternary lipid bilayers, including saturated lipids with between 12 and 20 carbons per tail. Coarse-grained molecular dynamics simulations reveal a novel two-step kinetics due to hydrophobic mismatch, in which the initial response of the apposed leaflets upon quenching is to increase local asymmetry (antiregistration), followed by dominance of symmetry (registration) as the bilayer equilibrates. Antiregistration can become thermodynamically preferred if domain size is restricted below ∼20 nm, with implications for the symmetry of rafts and nanoclusters in cell membranes, which have similar reported sizes. We relate our findings to theory derived from a semimicroscopic model in which the leaflets experience a "direct" area-dependent coupling, and an "indirect" coupling that arises from hydrophobic mismatch and is most important at domain boundaries. Registered phases differ in composition from antiregistered phases, consistent with a direct coupling between the leaflets. Increased hydrophobic mismatch purifies the phases, suggesting that it contributes to the molecule-level lipid immiscibility. Our results demonstrate an interplay of competing interleaflet couplings that affect phase compositions and kinetics, and lead to a length scale that can influence lateral and transverse bilayer organization within cells.
authors: Department of Biochemistry, University of Oxford , South Parks Road, Oxford, OX1 3QU, U.K.
authors: Philip W
authors: PW
authors: Fowler
authors: Department of Physics, Institute for Soft Matter Synthesis and Metrology, Georgetown University , 37th and O Streets, N.W., Washington, D.C. 20057, United States.
authors: John J
authors: JJ
authors: Williamson
authors: Department of Biochemistry, University of Oxford , South Parks Road, Oxford, OX1 3QU, U.K.
authors: Mark S P
authors: MS
authors: Sansom
authors: Department of Physics, Institute for Soft Matter Synthesis and Metrology, Georgetown University , 37th and O Streets, N.W., Washington, D.C. 20057, United States.
authors: Peter D
authors: PD
authors: Olmsted
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation
chemical_list: D008051:Lipid Bilayers; D008563:Membrane Lipids