Tetraether Archaeal Liposomes

智力优势：该提案阐述了由嗜热微生物（古细菌）提取的脂质制成的脂质体的性质。 这些不寻常的脂质包括两个疏水烃链，通过醚键连接在每一端的甘油部分。 每个末端的第三个（末端）甘油羟基带有一个通常是糖基的甘油基，可以被磷酸化，也可以不被磷酸化。 这些脂质形成单层膜和脂质体，称为四醚古菌脂质体（TAL），其中每个脂质分子的烃部分的两条链跨越整个膜厚度。 烃链基本上是用甲基定期修饰的直链烷烃。 在每一个这样的链中，可能有多达四个环戊烷基，这取决于细菌生长的温度;在较高温度下生长的细菌具有更多的环戊烷环。 与其他脂质体系统相比，所得脂质体显示出对温度、pH梯度、机械应力、压力和环境化学特征变化的显著抗性。 本项目旨在验证以下假设：（1）古细菌脂质中环戊烷环数量的增加将增加膜的刚性和紧密性，（2）囊泡曲率的变化将引起跨膜不对称性的变化，从而改变膜包装，（3）存在最佳的膜组成和糖含量，将产生最稳定的TAL结构。 为了验证这些假设，将使用各种物理技术，如动态光散射，高压探针技术，荧光光谱，量热法和电子显微镜。更广泛的重要性：TAL对温度，pH值和其他“应力”非常稳定，因此显示出作为靶向载体，药物递送剂和涂层的巨大前景。 它们代表了一类新的可高压灭菌的单层包封剂，具有可编程的稳定性和渗透性。 在过去的13年里，PI在他的实验室里培训了30多名来自代表性不足群体的本科生。 他将继续支持本科生参与这项新项目的研究。 他还参加了坦普尔大学为少数民族高中生举办的医生科学家培训项目，在过去的四年里，他接待了八名这样的学生。 这项活动也将在新的赠款下继续进行。

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.