Modulation of membrane architecture and function by physiologically relevant and toxic ions

点击翻译按钮获取中文摘要

Toxic metals are at the core of significant and growing concerns to the Natural Sciences and Engineering fields in Canada and beyond. Indeed, ion mixtures of toxic metals disrupt physiology via mechanisms that remain poorly understood. In accord with my long term research interest in the structure and function of biomembranes, this proposal addresses the impact of ions and toxic metals on membranes. The impact of essential ions Na+, K+ and Ca++ is compared with the common pollutants Cd++ and Hg++. Ion combinations are important since the human body is exposed to a mix of pollutants which may increase their effects. These ions differ in their toxicity as Cd++ was reported as a problem for wildlife whereas Hg++ is more a concern for domestic animals. Ion-membrane interactions are studied in four areas: i) ion binding to the surface: Using a novel assay we have shown that Hg++ preferred negatively charged phosphatidylserine (PS) whereas Cd++ interacted stronger with zwitterionic phosphatidylethanolamines. ii) impact on membrane dynamics: The interaction of toxic divalent ions often decreased membrane fluidity and increased of membrane permeability which both effect cellular function. A comprehensive analysis in terms of lipid composition and the use of ion mixtures is proposed. iii) impact on membrane organization: Ions can impact the lipid phase behavior and induce clustering of lipids as seen for the interactions of Ca++ and PS whereby resulting patches bind proteins. iv) impact on red blood cells and extracts: Model systems will be compared with biological extracts and blood cells. Changes of the characteristic discoidal shape of red blood cells by Cd++ and Hg++ have been reported but not in a concentration dependant manner or after exposure to ion mixtures. The proposed work is significant as a comprehensive investigation of the impact of ions on biomembranes. A better understanding of the basic biological principles may help to uncover better means to control the effects of pollutants on wildlife, livestock and indeed public health.