Includes bibliographical references. / 189 leaves, 18, [4] pages : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physical and Inorganic Chemistry, 1991

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (p. 92-102).

Call number: LD2668 .T4 1984 G664 / Master of Science

No description available.

Anesthesia, a state of being absent of sensation and consciousness, has been recognized since antiquity. Even today anesthesia is still best characterized by the lack of consciousness and sensations. Since anesthetic potency is correlated with lipid solubility, the site of action of general anesthetics has been thought to be hydrophobic in nature and to involve excitable membranes critical for interneuronal communications. Thus, general anesthetics may interact directly with functionally-relevant membrane proteins (via hydrophobic pockets) or indirectly, with the lipids surrounding these proteins. To better understand the details of general anesthetic action, I examined how halothane interacts with a functional synaptic protein, the acetylcholine receptor channel embedded in the membranes of cultured Xenopus myocytes. Next, I examined how changing the lipid composition, of these membranes, affected this interaction. Using the extracellular patch-clamp technique, I found that halothane, at clinically-relevant concentrations, shortened the burst duration of single receptor channels without affecting their conductance. Moreover, the halothane-induced reduction of burst durations was significantly attenuated after pretreatment with cholesterol-rich lipsomes which increased significantly the cholesterol content of these cells. These findings provide the first direct support for the role of membrane lipids in the mechanism of GA action. In particular, I demonstrated that increases in membrane cholesterol antagonize the anesthetic action of halothane. Although direct action of cholesterol on synaptic proteins cannot be ruled out, my data strongly suggest that membrane lipids are involved at a critical, but as yet undefined, site with which GAs interact. The exact manner by which increases in membrane cholesterol antagonize GA action remains to be eludicated.

The purpose of this research was to determine if a high cholesterol diet can affect tie rate of cholesterol synthesis or to cholesterol and fatty acid content of plasma membranes of mouse mammary a.denocarcinoma and normal mouse mammary gland tissue.Cholesterol synthesizing ability was determined by measuring the incorporation of 14C acetate into digitonin-precipitable sterols from both tumors and normal mammary tissue from Strong A Strain female mice fed a standard lab chow diet (control diet; or a 2% cholesterol experimental diet. Plasma membranes were isolated from both tenors and normal tissue by differential centrifugation. Cholesterol was measured spectrophotometrically. Fatty acids were extracted, methylated, and methylesters identified and quantified using gas liquid chromatography.The rate of incorporation of 111C acetate into digitonin-precipitated sterols in normal mammary tissue from mice fed the 2% cholesterol experimental diet was 1.5 times less than controls. Tumor tissue showed no significant difference. The fatty acid composition of tumor and normal mammary tissue plasma membranes from mice fed the 2% cholesterol experimental diet was similar to controls.There were higher percentages of C16:0 and C16.1 in normal plasma membranes of controls than mice fed the experimental diet. Cholesterol content of to or and normal mammary tissue plasma membranes from mice fed the experimental diet was similar to controls.It would appear that dietary cholesterol does have an effect on cholesterol synthesis in normal mammary tissue but not in marina y tumor tissue. Also dietary cholesterol does not have an effect on the fatty acid composition nor the cholesterol content in plasma membranes of mammary tumors or normal mammary tissue.Ball State UniversityMuncie, IN 47306

Antimicrobial peptides (AMPs) are not only fast microbe-killing molecules deployed in the host defense of living organisms but also offer valuable lessons for developing new therapeutic agents. While the mode of action of AMPs is not clearly understood yet, membrane perturbation has been recognized as a crucial step in the microbial killing mechanism of many AMPs. In this thesis, we first present a physical basis for the selective membrane-disrupting activity of cationic AMPs. To this end, we present a coarse-grained physical model that approximately captures essential molecular details such as peptide amphiphilicity and lipid composition (e.g., anionic lipids). In particular, we calculate the surface coverage of peptides embedded in the lipid headgroup-tail interface and the resulting membrane-area change, in terms of peptide and membrane parameters for varying salt concentrations. We show that the threshold peptide coverage on the membrane surface required for disruption can easily be reached for microbes, but not for the host cell -- large peptide charge (≳4) is shown to be the key ingredient for the optimal activity-selectivity of AMPs (in an ambient-salt dependent way). Intriguingly, we find that in a higher-salt environment, larger charge is required for optimal activity. Inspired by membrane softening by AMPs, we also study electrostatic modification of lipid headgroups and its effects on membrane curvature. Despite its relevance, a full theoretical description of membrane electrostatics is still lacking -- in the past, membrane bending has often been considered under a few assumptions about how bending modifies lipid arrangements and surface charges. Here, we present a unified theoretical approach to spontaneous membrane curvature, C₀, in which lipid properties (e.g., packing shape) and electrostatic effects are self-consistently integrated. Our results show that C₀ is sensitive to the way lipid rearrangements and divalent counterions are modeled. Interestingly, it can change its sign in the presence of divalent counterions, thus stabilizing reverse hexagonal (H_II) phases.

Thesis (M.Sc.), Memorial University of Newfoundland, 2000. / Bibliography: leaves 115-118.

Thesis (Ph. D.)--University of Chicago, Department of Physics, December 2003. / CD-ROM includes PDF files of figures 2.1-4.7. Includes bibliographical references. Also available on the Internet.

The work described here has focused on two types of supramolecular assemblies, supported lipid bilayers (SLBs) and giant vesicles (GVs) from polymerizable lipids. SLBs are explored extensively as structural models in biophysical studies of cell membranes and biosensor coatings. With regard to implementation as biocompatible scaffoldings for receptor-based molecular devices, fluid SLBs lack chemical, thermal and mechanical stability as lipids are self-organized by weak, noncovalent forces. One possible solution is to use synthetic lipid monomers that can be polymerized to form robust bilayers. A key question is how polymerization affects transmembrane protein structure and activity. Specifically it is unclear if lipid cross-linking can be achieved without adversely affecting the activity of incorporated proteins. In this work the effect of lipid polymerization on transmembrane protein activity was studied with rhodopsin. The protein was reconstituted into SLBs composed of polymerizable lipids, bis-SorbPC, bis-SorbPC:mono-SorbPC, bis-DenPC and bis-SorbPC:mono-SorbPE. Rhodopsin photoactivity was monitored using plasmon waveguide spectroscopy. The results show that reconstitution of rhodopsin into SLBs composed of phosphatidylcholine with the polymerizable moiety in the acyl chain terminus, followed by photoinduced cross-linking of the lipids, does not significantly perturb protein function. A possible explanation is that a bilayer with relatively low Xn retains sufficient elasticity to accommodate the membrane deformation that accompanies the conformational change associated with rhodopsin photoactivation when polymerized in the acyl chain terminus. GVs have diameters ranging from several to few hundred micrometers and thus can be observed by optical microscopic methods. This allows manipulation of individual vesicles and observation of their transformations in real time. GVs have attracted attention as microcontainers for enzymes and drugs, and as biosensors. With the aim of increasing stability for these types of applications, GVs were prepared from synthetic dienoyl lipids that can be polymerized to form robust vesicles. The stability of these vesicles after polymerization was investigated by surfactant treatment, drying and rehydration, and temperature variations. The structure of poly(GVs) was largely retained under these conditions which destroy unpolymerized vesicles. Permeability studies on poly(GVs) suggests that they could be potentially used in a variety of technological applications, including sensors, macromolecular carriers, and microreactors.