Tetraether Archaeal Liposomes

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INTELLECTUAL MERIT: This proposal addresses the properties of liposomes made from lipids extracted from thermophylic microorganisms (archaea). These unusual lipids involve two hydrophobic hydrocarbon chains attached at each end through ether linkages to a glycerol moiety. The third (terminal) glycerol hydroxyl at each end carries a hydrophylic group that is frequently sugar based and may or may not be phosphorylated. These lipids form monolayer membranes and liposomes, termed tetraether archaeal liposomes (TAL), in which the two chains of the hydrocarbon portion of each lipid molecule span the entire membrane thickness. The hydrocarbon chains are essentially linear alkanes decorated periodically with methyl groups. Within each such chain there may be up to four cyclopentanyl groups, depending on the temperature at which the bacteria are grown; those grown at higher temperatures have greater numbers of cyclopentane rings. In comparison to other liposome systems, the resulting liposomes show remarkable resistance to changes in temperature, pH gradient, mechanical stress, pressure, and chemical features of the environment. This project is designed to test the following hypotheses: (1) an increase in the number of cyclopentane rings in archaeal lipids will increase membrane rigidity and tightness, (2) a change in vesicle curvature will induce a change in transmembrane asymmetry, which in turn changes membrane packing, (3) there exist optimal membrane compositions and sugar contents that will yield the most stable TAL structures. To test these hypotheses, a variety of physical techniques such as dynamic light scattering, high-pressure probe techniques, fluorescence spectroscopy, calorimetry, and electron microscopy will be used.BROADER IMPACTS: TAL are remarkably stable to temperature, pH, and other 'stresses', and therefore show great promise as targeted carriers, drug delivery agents, and coatings. They represent a new class of autoclavable monolayer encapsulating agents with programmable stability and permeability. The PI has trained more than 30 undergraduate students from under represented groups in his laboratory in the past 13 years. He will continue to support undergraduate research participation under this new project. He also participates in the Temple University Physician Scientist Training Program for minority high school students, and he has hosted eight such students in the past four years. This activity will also continue under the new grant.