Atomistic Simulations of Bicelle Mixtures

Abstract

Mixtures of long- and short-tail phosphatidylcholine lipids are known to self-assemble into a variety of aggregates combining flat bilayerlike and curved micellelike features, commonly called bicelles. Atomistic simulations of bilayer ribbons and perforated bilayers containing dimyristoylphosphatidylcholine (DMPC, di-C(14) tails) and dihexanoylphosphatidylcholine (DHPC, di-C(6) tails) have been carried out to investigate the partitioning of these components between flat and curved microenvironments and the stabilization of the bilayer edge by DHPC. To approach equilibrium partitioning of lipids on an achievable simulation timescale, configuration-bias Monte Carlo mutation moves were used to allow individual lipids to change tail length within a semigrand-canonical ensemble. Since acceptance probabilities for direct transitions between DMPC and DHPC were negligible, a third component with intermediate tail length (didecanoylphosphatidylcholine, di-C(10) tails) was included at a low concentration to serve as an intermediate for transitions between DMPC and DHPC. Strong enrichment of DHPC is seen at ribbon and pore edges, with an excess linear density of approximately 3 nm(-1). The simulation model yields estimates for the onset of edge stability with increasing bilayer DHPC content between 5% and 15% DHPC at 300 K and between 7% and 17% DHPC at 323 K, higher than experimental estimates. Local structure and composition at points of close contact between pores suggest a possible mechanism for effective attractions between pores, providing a rationalization for the tendency of bicelle mixtures to aggregate into perforated vesicles and perforated sheets.

Rapid, Reversible Release from Thermosensitive Liposomes Triggered by Near‐Infra‐Red Light

“…However, liposomes with 15 mol% MPPC are polygonal with sharper edges between the facets. This suggests that the MPPC is segregated to the high curvature regions at the grain boundaries . Increasing MPPC to 20 mol% destabilized the liposomes and led to coexistence between bilayer discs (arrows) and intact liposomes …”

“…TSL have a membrane composition designed to induce a step change in permeability in response to modest changes in temperature above 37 °C . Needham, Dewhirst and co‐workers pioneered lyoslipid‐TSL formulations, which in addition to dipalmitoylphosphatidylcholine (DPPC), contain lysolipid and lipid‐conjugated PEG 2000 (DSPE‐PEG 2000 ); experiments and computer simulations suggest that the permeability transition is due to the formation of lysolipid‐stabilized transient pores that occur at the phase transition temperature of DPPC ( Figure ) . TSL have shown improved efficacy with a number of cancer cell lines in vitro and in vivo, and clinical trials are ongoing for treatment of liver and breast cancers with combined hyperthermia and TSL .…”

When detergent meets bilayer: Birth and coming of age of lipid bicelles

“…Only recently, two atomistic simulations on bilayer ribbons were reported which provide insight into lipid behavior in bicelles: the effect of bilayer edge and curvature on the partitioning of lipids by tail lengths was investigated [168]. A two-step semi-grand-canonical mixed Monte Carlo/molecular dynamics approach found a possible mechanism for attraction and merging of DHPC pores [169]. The three-dimensional structure of glycolipids embedded in bilayers starts to be investigated by combined use of isotropic bicelle NMR experiments and molecular dynamics simulations [320].…”

On the Role of NMR Spectroscopy for Characterization of Antimicrobial Peptides

“…At high detergent concentrations ( q ~ 0.1 – 0.8), bicelles assume a discoidal shape and tumble rapidly in solution. At low detergent concentrations ( q ~ 2.8 – 6), bicelles may resemble perforated bilayer sheets (123–125). While AMPs and membrane proteins can be analyzed by solution NMR techniques in isotropic bicelles, anisotropic bicelles align spontaneously in magnetic fields, enabling peptides and proteins to be analyzed using oriented solid-state NMR approaches (126–130).…”