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Large Scale Conformational Transitions

Large Scale Conformational Transitions

Large scale conformational transitions can occur in lipid bilayers.  These include bud formation, formation of vesicles which split off from the membrane, and fusion of membrane vesicles, all of which are important biologically.  To some extent, the tendency to engage in these larger shape transitions depends on the local curvature of the vesicle, which depends on the local phospholipid composition and fluidity of the membrane.  We have previously seen that segregation of lipids into rafts (or domains) within a leaflet depends on the phospholipid content.  Baumgart et al. have made giant unilamellar vesicles (GUV) containing a mixture of three lipids: sphingomyelin (SM), dioleylphosphatidylcholine (DOPC), and cholesterol (C) to study transitions in the bilayers.  SM and C segregate laterally into a "liquid phase" domain characterized by significant order (Lo) while DOPC forms a "liquid phase" with more disorder (Ld).  They could detect the different phases through fluorescence microscopy of GUV's labeled with fluorophores (molecules that absorb visible or UV light and emit photons of lower energy (higher wavelength).  The first, N-lissamine rhodamine dipalmitoylphosphatidylethanolamine (red fluorescence), partitions almost exclusively into the Ld phase.  The second, perylene (blue fluorescence), partitioned with great selectivity into the Lo phase.  The results of their studies are shown in the figures below.  This images provide stunning visualization of lipid domains (rafts) including those in the shapes of circles, stripes, and rings.  Their works shows that the boundary between the domains is important in determining lipid structures.  Structures are favored which reduce the perimeter at the boundaries of the phases.  It appears that the Ld phase (and associated lipids) is found preferentially in area of high membrane curvature, while the Lo phase is found is regions of lower curvature.  The two figures below are reprinted with permission of Nature and the authors:   Baumgart,  Hess,  and Webb, W. Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension.  Nature. 425, pg 821 (2003)

Figure:  Equatorial cross sections of GUVs with multiple phases

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 Figure: GUVs structures with multiple phases

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Movie:  Molecular Dynamics Simulation of vesicle fusion (scroll down to 52:  Control of Membrane Fusion Reaction..)