Effect of cytochrome c on the phase behavior of charged multicomponent lipid membranes.
We studied the effect of submicromolar concentrations of cytochrome c (cyt c) on the phase behavior of ternary lipid membranes composed of charged dioleoylphosphatidylglycerol, egg sphingomyelin and cholesterol. The protein was found to induce micron-sized domains in membranes belonging to the single-fluid-phase region of the protein-free ternary mixture and, as a result, to expand the region of coexistence of liquid ordered (Lo) and liquid disordered (Ld) phases. Direct observations on individual vesicles revealed that protein adsorption increases the area of Ld domains. Measurements using a fluorescent analog of cyt c showed that the protein preferentially adsorbs onto domains belonging to the Ld phase. The adsorption was quantitatively characterized in terms of partitioning ratios between the Ld and the Lo phases. The protein was also found to induce vesicle leakage even at relatively low concentrations. In eukaryotic cells under normal physiological conditions, cyt c is localized within the intermembrane space of mitochondria. During cell apoptotis, cyt c is released into the cytosol and its adsorption to intracellular membranes may strongly perturb the lipid distribution within these membranes as suggested by our results.
Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14424 Potsdam, Germany.
Salome
S
Pataraia
Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14424 Potsdam, Germany; State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022 Changchun, China.
Yonggang
Y
Liu
Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14424 Potsdam, Germany.
Reinhard
R
Lipowsky
Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14424 Potsdam, Germany. Electronic address: Rumiana.Dimova@mpikg.mpg.de.
Rumiana
R
Dimova
D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D045304:Cytochromes c / Q000494:pharmacology*; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism*; D018613:Microscopy, Confocal; D044367:Phase Transition / Q000187:drug effects*; D010715:Phosphatidylglycerols / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
D008563:Membrane Lipids; D010715:Phosphatidylglycerols; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol; D045304:Cytochromes c; D002784:Cholesterol
Cholesterol; Confocal microscopy; DOPG; Egg sphingomyelin; Giant vesicles; Phase diagram (Gibbs triangle)