142 leaves : graphs ; 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 Mathematical Physics, 1980

Biological cells and subcellular organelles are surrounded by membranes to form compartments performing specialized functions. Adsorption or partitioning of biologically active compounds into the membrane is the first step in the process of modification of cell function. This work is concerned with the problem of distribution of charged molecules between water and electrically charged membrane surface and between water and octanol. Part I of this thesis is focused on the electrostatic interactions taking place between charges on the membrane and ions present in the aqueous region of the membrane/water interface. The objective was to explore theoretically the origin of anomalous behavior of Ruthenium Red (RuR), a positively charged hexavalent ion. It was discovered in studies of RuR adsorption to negatively charged membranes that within the framework of the Gouy-Chapman theory of the membrane/water interface, RuR behaves as an ion with effective charge less than its physical charge. Moreover, the effective charge was found to be dependent on the density of electric charge at the membrane surface. Two theoretical models of the interfacial region were examined: the Rod Model and the Maximum Density Model. The Rod Model takes into account steric constraints imposed on RuR at the vicinity of the membrane surface. The Maximum Density Model attempts to account for non-ideal behavior by including repulsive interactions. These theoretical studies illustrate the consequences of finite size and ion-ion interactions of adsorption of large molecular ions to electrically charged membrane surfaces. Part II is an experimental study whose objective was to determine the partition coefficient of the negatively charged 2,3,4,5-tetrachlorophenol (TeCP) between water and octanol. The study was based on spectrophotometric measurements of the equilibrium concentrations of TeCP in water and octanol as a function of pH. The octanol/water partition coefficient for both the non-ionized and ionized species of TeCP were determined. It was found that the partition coefficient of ionized TeCP to lipid membrane is about 400 times greater than that for octanol. This result supports the hypothesis that the octanol/water partition coefficient of ionized chlorophenols cannot be used for predicting their distribution between water and lipid-bilayercontaining elements of the environment.

During a traumatic insult to the brain, tissue is subjected to large stresses at high rates which often surpass cellular thresholds leading to cell dysfunction or death. Cellular events that occur at the time of and immediately after an insult are poorly understood. Immediately following traumatic brain injury (TBI), the neuronal plasma membrane may become disrupted and potentiate detrimental pathways by allowing extracellular contents to gain access to the cytosol. In the current study, neuronal plasma membrane disruption was assessed in vivo following moderate unilateral controlled cortical impact in rats using a normally cell-impermeant fluorescent compound as a plasma membrane permeability marker. This fluorescent dye was injected into the cerebrospinal fluid and was allowed to diffuse into the brain. TBI caused a widespread acute disruption of neuronal membranes which was significantly different compared to uninjured brains. Affected cells were present in cortex and hippocampal regions. These findings were complemented by an in vitro model of TBI where membrane disruption was quantified and its mechanisms elucidated. Permeability marker(s) were added to neuronal cultures before the insult as indicators for increases in plasma membrane permeability. The percentage of cells containing the permeability marker was dependent on the molecular mass, as smaller molecules gained access to a higher percentage of cells than larger ones. Permeability increases were also positively correlated with the rate of insult. Membrane disruption was transient, evidenced by a robust resealing within the first minute after the insult. In addition, membrane resealing was found to be dependent on extracellular Ca2+, as chelation of the ion abolished a significant amount of resealing. We have also investigated the effects of mechanically-induced plasma membrane disruptions on neuronal network electrical activity. We have developed a multielectrode array system that allows the study of electrical activity before, during, and after a traumatic insult to neurons. Endogenous electrical activity of neuronal cultures presented a heterogeneous response following mechanical insult. Moreover, spontaneous firing dysfunction induced by injury outlasted the presence of membrane disruptions. This study provides a multi-faceted approach to elucidate the role of neuronal plasma membrane disruptions in TBI and its functional consequences.