A series of structural studies is proposed to obtain information on the interaction of lipid bilayers with three of the principal components of biological membranes--water, cholesterol, and carbohydrates. These X-ray diffraction, neutron diffraction and freeze-fracture electron microscopy experiments are designed to give precise details concerning effects these molecules have on bilayer structure, particularly in the interfacial region, and to help characterize their functional roles in membranes. Our experiments should provide data relevant to the molecular mechanisms of membrane transport processes, cell aggregation, cell adhesion and cell fusion. One project will focus on the depth of water penetration in fully hydrated bilayers and the influence that cholesterol and other biologically active molecules, such as ergosterol and phloretin, have on the water/bilayer interface. A second project is to experimentally test two major theoretical models of the repulsive hydration force. This force, which is present in all drug-receptor interactions and between all cell membranes, will be analyzed by measuring the force and distance between bilayers in the presence of non-electrolytes which have different dimensions and dielectric properties than water. The long-range attractive force will be studied in a similar manner to determine whether the Lifshitz formalism can satisfactorily explain all long-range attractive interactions between membranes. In addition we propose to study the properties of an unusual lamellar phase where the hydrocarbon chains of apposing monolayers interpenetrate or interdigitate. This phase will be very useful in testing theoretical models for the repulsive and attractive forces, since the interdigitated phase has twice the area per molecule of a normal lamellar phase.
| McIntosh, Thomas J (2015) Stepping between membrane microdomains. Biophys J 108:783-784 |
| Tong, Jihong; Canty, John T; Briggs, Margaret M et al. (2013) The water permeability of lens aquaporin-0 depends on its lipid bilayer environment. Exp Eye Res 113:32-40 |
| Zhang, Xiao-Xiang; McIntosh, Thomas J; Grinstaff, Mark W (2012) Functional lipids and lipoplexes for improved gene delivery. Biochimie 94:42-58 |
| Godeau, Guilhem; Navailles, Laurence; Nallet, Frédéric et al. (2012) From Brittle to Pliant Viscoelastic Materials with Solid State Linear Polyphosphonium - Carboxylate Assemblies. Macromolecules 45:2509-2513 |
| Tong, Jihong; Briggs, Margaret M; McIntosh, Thomas J (2012) Water permeability of aquaporin-4 channel depends on bilayer composition, thickness, and elasticity. Biophys J 103:1899-908 |
| LaManna, Caroline M; Lusic, Hrvoje; Camplo, Michel et al. (2012) Charge-reversal lipids, peptide-based lipids, and nucleoside-based lipids for gene delivery. Acc Chem Res 45:1026-38 |
| Picazo-Juárez, Giovanni; Romero-Suárez, Silvina; Nieto-Posadas, Andrés et al. (2011) Identification of a binding motif in the S5 helix that confers cholesterol sensitivity to the TRPV1 ion channel. J Biol Chem 286:24966-76 |
| Zhang, Xiao-Xiang; Prata, Carla A H; Berlin, Jason A et al. (2011) Synthesis, characterization, and in vitro transfection activity of charge-reversal amphiphiles for DNA delivery. Bioconjug Chem 22:690-9 |
| Zhang, Xiao-Xiang; Prata, Carla A H; McIntosh, Thomas J et al. (2010) The effect of charge-reversal amphiphile spacer composition on DNA and siRNA delivery. Bioconjug Chem 21:988-93 |
| Rosenbaum, Tamara; Simon, Sidney A; Islas, Leon D (2010) Ion channels in analgesia research. Methods Mol Biol 617:223-36 |
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