Phase diagram of a 4-component lipid mixture: DSPC/DOPC/POPC/chol

Abstract

We report the first 4-component phase diagram for the lipid bilayer mixture, DSPC/DOPC/POPC/chol (distearoylphosphatidylcholine/dioleoylphosphatidylcholine/1-palmitoyl, 2-oleoylphosphatidylcholine/cholesterol). This phase diagram, which has macroscopic Ld+Lo phase domains, clearly shows that all phase boundaries determined for the 3-component mixture containing DOPC transition smoothly into the boundaries for the 3-component mixture containing POPC, which has nanoscopic phase domains of Ld+Lo. Our studies start from two published ternary phase diagrams, and show how these can be combined into a quaternary phase diagram by study of a few hundred samples of intermediate compositions.

Keywords: 1,1′-didodecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate; 1,1′-dieicosanyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate; 1,2-Dilauroyl-sn-glycero-3-phosphocholine; 1,2-Dioleoyl-sn-glycero-3-phosphocholine; 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine; 1,2-Distearoyl-sn-glycero-3-phosphocholine; 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine; 1-Stearoyl-2-oleoyl-sn-glycero-3-phosphocholine; 2-(4,4-Difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine; 3-Dye method; 4-Component lipid phase diagram; BoDIPY-PC; C12:0-DiI; C20:0-DiI; Chol; Cholesterol; Competing interaction; DHE; DLPC; DOPC; DPPC; DSPC; Ergosta-5,7,9(11),22-tetraen-3β-ol; FRET; Förster resonance energy transfer; GUV; Giant unilamellar vesicle; LHS; Left hand side refers to left side of phase diagram, i.e. at lower χ(DSPC); Lipid raft; Modulated phase; PC; POPC; Phosphatidylcholine; Quaternary phase diagram; REE; RHS; RRE; RSE; Rapid solvent exchange; Region of enhanced efficiency; Region of reduced efficiency; Right hand side, refers to right side of phase diagram, i.e.,, at higher χ(DSPC); SAE; SM; SOPC; Sensitized acceptor emission; Sphingomyelin; T1–T6; TLC; TOE; Thin-layer chromatography; Trajectories 1–6. bSM, sphingomyelin derived from porcine brain; Trp-Oleoyl Ester, N-oleoyl-dl-tryptophan ethyl ester.