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No / Dimethylsulfoxide (DMSO) is an aprotic solvent that has the ability to induce cell fusion and cell differentiation and enhance the permeability of lipid membranes. It is also an effective cryoprotectant. Insights into how this molecule modulates membrane structure and function would be invaluable toward regulating the above processes and for developing chemical means for enhancing or hindering the absorption of biologically active molecules, in particular into or via the skin. We show here by means of molecular simulations that DMSO can induce water pores in dipalmitoyl-phosphatidylcholine bilayers and propose this to be a possible pathway for the enhancement of penetration of actives through lipid membranes. DMSO also causes the membrane to become floppier, which would enhance permeability, facilitate membrane fusion, and enable the cell membrane to accommodate osmotic and mechanical stresses during cryopreservation.

The bioorthogonal copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction exhibits complex but well-defined kinetics in aqueous and organic solution for soluble azides, alkynes, and ligand-bound copper(I). The kinetic profile in two dimensions, however, for CuAAC systems within a lipid bilayer membrane, has yet to be defined. The effect of triazole formation with lipid membrane-bound components on membrane properties such as fluidity and permeability is also of interest. Azide- and alkyne-functionalized lysolipids were synthesized and incorporated into non-fluid vesicles, which were then subject to CuAAC. The rate order for membrane-bound lipid substrates in non-fluid vesicles was observed to be comperable to that of the reaction in solution. Reactions between vesicles showed evidence of lipid transfer between non-fluid membranes, which has not been previously reported. For intervesicular and intravesicular reactions in non-fluid membranes, the observed reactivity was found to be opposite that of previously published reactions between nucleophiles and electrophiles in fluid lipid systems. Applications of this work include the potential for novel symmetric membrane leaflet labeling, bioorthogonal manipulation of cell and tissue function, and the creation of membranes with precisely controlled properties that may not be available in naturally-occurring membranes.

Thesis (Ph.D.) -- Flinders University, School of Medicine, Dept. of Paediatrics and Child Health. / Typescript (bound). Includes bibliographical references (leaves 186-203). Also available online.

Thesis (M.S.)--University of Delaware, 2009. / Principal faculty advisor: Sandeep Patel, Dept. of Chemistry & Biochemistry. Includes bibliographical references.

Thesis (M.S.)--University of North Carolina Wilmington, 2008. / Title from PDF title page (viewed September 24, 2008) Includes bibliographical references (p. 58-59)

Interactions of engineered nanomaterials (ENMs) with environmental interfaces have become a critical aspect of environmental health and safety evaluations. Carbon fullerene (C₆₀) has emerged at the forefront of nanoscale research and applications due to its unique properties. Although there are concerns associated with the harmful effects of fullerene towards living organisms, the mechanisms of fullerene toxicity are still under debate. A first step toward assessing these mechanisms requires evaluation of the bio-accumulation and bio-uptake of fullerene through lipid membranes which serve as biological barriers in cells. In this dissertation, partitioning of fullerene between water and lipid membranes and cellular uptake of fullerene were investigated to assess bioavailability of this nanoparticle. Traditional methods to estimate the equilibrium partitioning of molecular level chemicals between water and lipid membranes (K[subscript lipw]) cannot be applied to measure K[subscript lipw] of nanoparticles due to the large size of nanoparticle aggregates. In this study, we developed an in vitro method to estimate K[subscript lipw] of fullerene using solid supported lipid membranes (SSLMs) with various membrane compositions. K[subscript lipw] of fullerene increased with increasing acyl chain length and K[subscript lipw] values were higher after creating phase separation in ternary lipid membranes compared to pre-phase separation. In addition, the partitioning values (K[subscript lipw]) were found to depend on the lipid head charges. These results suggest that the lipid membrane composition can be a critical factor for assessing bioaccumulation of fullerene. Evaluation of the partitioning thermodynamics of fullerene demonstrated that the partitioning mechanism of fullerene is different from that of molecular level chemicals. It is generally acknowledged that molecular level chemicals partition into the hydrophobic center of lipid membranes (i.e., absorption), however, the partitioning mechanism of fullerene is a combination of adsorption on the lipid membrane surface and absorption. Caco-2 cellular uptake of fullerene nanoparticles was investigated using an in vitro method developed in this study to distinguish between active and passive transport across cell membranes. Energy dependent endocytosis is hypothesized to be the main cellular transport mechanism based on an observed temperature dependence of cellular uptake and evidence for saturation of the active sites of transport during cellular uptake of fullerene. Metabolic inhibitors decreased the mass of fullerene taken up by the cells, which supports an active transport mechanism of fullerene through the cell membranes. To evaluate bioavilability of fullerene under environmentally relevant conditions, the effects of humic acid and fetal bovine serum (FBS) on the lipid accumulation and cellular uptake were also investigated. Humic acid and FBS changed the surface characteristics of fullerene. The presence of FBS significantly decreased lipid accumulation of fullerene presumably due to higher steric hinderance of FBS coated fullerene as well as the changes in surface energy, water solubility, and lipid solubility of charged FBS coated fullerene relative to that of bare fullerene. Both humic acid and FBS also effectively lowered the cellular uptake of fullerene. These results imply that natural organic matter and biomolecules in natural aquatic and biological environments have significant effects on the bioavilability of fullerene nanoparticles / text

Photocopy of typescript. / Digitized by Kansas Correctional Industries

Includes bibliographical references (leaves 169-184) / xiv, 184 leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the concept of membrane homeostatis, which implies that biological membranes tend to maintain a constant level of lipid fluidity in the face of potential exogenous and endogenous pertubations. Manipulations of dietary cholesterol and/or saturated (coconut oil) v/s unsaturated (sunflower seed oil) fatty acids have been used to study the relationship between membrane lipid composition, membrane lipid fluidity and membrane-bound enzymes of lipid metabolism; and, to see whether these enzymes act co-ordinately for the maintenance of a membrane homeostatis under these dietary conditions. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Sciences, 1986

Thesis (M.Sc.)--Memorial University of Newfoundland, 2005. / Bibliography: leaves 86-96.