Membrane Molecular Organization

Compositional Heterogeneity, Domains, and Interfaces

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Lipid Rafts and Cholesterol-enriched micro-domains

Simons, K. & Ikonen, E. Cell biology - How cells handle cholesterol. Science 290, 1721-1726 (2000).

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curvature-dependent domain organization and superstructure formation.

A cartoon depiction


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domain-domain alignment

interlamellar stacking of cholesterol-rich micro-domains

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lipid organization at the bud collar rim

Spatio-Temporal Organization of Membrane Components

Cellular lipidome consists of at least 9600 distinct species of glycerosphingolipids, more than 100,000 species of sphingolipids, and many fatty acids and sterol based components. This enormous compositional complexity naturally raises a fundamental question: how are membrane components organized? A simple application of Gibb’s phase rule (P= C-F+2, where P, C, and F represents number of independent phases, components, and variables respectively) predicts an unusually large number of co-existing phases within the equilibrated membrane milieu. Experimentally, however, the number of co-existing phases in cellular membranes is almost invariably limited. This is because the membrane’s compositional heterogeneity is reduced because membrane components do not exist as chemically independent species; rather preferential associations produce phase separated micro-domains and assemblages( Simons & Ikonen 2000).



Interestingly, the organization of molecular heterogeneities in membranes is not static: a wide variety of external physical and chemical perturbations readily shift the miscibility characteristics of membrane molecules. These phase-separating domains or “hot spots” have been long thought to spatially and temporally localize important biological functions (e.g., molecular recognition, cell-surface signaling, and transport)( Lingwood & Simons 2010)..

We have been studying the coupling of lateral phase separation of membrane components under a range of global physical perturbations including hydration-repulsion, imposed curvatures, induced tension, and interfacial adhesion.

We have also begun examining the coupling of membrane phase separation with local chemical perturbations including ligand binding, membrane protein incorporation, inter-membrane association, nanoparticle interactions, and non-specific interactions with amphipathic domains.

Selected References

Lingwood, D. & Simons, K. Lipid Rafts As a Membrane-Organizing Principle. Science 327, 46-50 (2010)..

Tayebi, L., Ma, Y., Vashaee, D., Sinha, S. & Parikh, A. N. Long-range interlayer alignment of intralayer domains in stacked lipid bilayers. Nature Materials 11, 1074-1080 (2012).

Sanii, B., Smith, A.M., Butti, R., Brozell, A.M. & Parikh, A.N. Bending membranes on demand: Fluid phospholipid bilayers on topographically deformable substrates. Nano Letters 8, 866-871 (2008)

Gilmore, S.F., Nanduri, H. & Parikh, A.N. Programmed Bending Reveals Dynamic Mechanochemical Coupling in Supported Lipid Bilayers. Plos One 6 (2011).

Ryu, Y.S. et al. Reconstituting ring-rafts in bud-mimicking topography of model membranes. Nat. Commun. 5, 8 (2014).