CAREER: Mineral Surface Mediated Organization of Biological Macromolecules

研究人员的总体职业愿景是开发一个研究计划，探索与生物地球化学(包括环境化学、生物矿化和地质医学)相关的过程中矿物表面与生物大分子的相互作用，并结合一项教育倡议，(I)提高公众对生物地球科学在他们生活中的影响的认识，(Ii)说明核心物理科学如何提供一种语言来解释外部环境或人体内的自然现象，以及(Iii)增加少数民族和妇女对物理科学的参与。本提案描述了职业生涯规划的一个主要部分。研究部分是研究磷脂在石英表面的独特吸附和自组装，并与其他氧化物进行比较。这项研究的动机是观察到，石英破裂细胞膜，主要由磷脂组成，而无定形二氧化硅、八面体结晶二氧化硅(辉钛矿)以及其他氧化物，如刚玉和锐钛矿，则相对良性。目前还没有令人满意的模型来解释矿物相的不同生物活性。初步的热力学模拟表明，氧化物的不同生物活性是由于与磷脂的水化相比，氧化物表面电荷和水化(亲水性)所反映的结晶学和化学组成的不同。表面电荷和水合作用的不同最终影响磷脂的吸附、自组装和组织或破裂的程度。这项拟议工作的一个主要目标是结合从头计算和合作实验工作来验证这一假说。结果可能对理解生命进化早期的细胞化、细胞与矿物表面的黏附、吸入粉尘对肺细胞的影响、设计生物兼容的医疗设备以及工业应用(如矿石加工过程中的生物富化)具有重要意义。将研究磷脂酰胆碱从水溶液中在石英、二氧化硅玻璃、斜长石和锐钛矿表面的吸附和自组装。还将考察pH值和本底电解液的影响。等温线和微量热法将提供吸附能。这些实验将与威斯康星大学麦迪逊分校(UW)生物化学系Anant Menon教授和Thomas Record教授合作进行。衰减全反射-傅里叶变换红外光谱(ATR-FTIR)光谱结合能量和振动频率的量子化学簇计算将表明磷脂的哪些特定官能团与矿物表面相互作用。磷脂自组装表面聚集体的形态变化反映了界面溶剂化的变化，将使用原子力显微镜进行监测。振动光谱学和原子力显微镜实验将与威斯康星州化学系罗伯特·哈默斯教授合作完成。作为职业生涯教育计划的一部分，在该项目期间，P.I.和她的研究小组将在威斯康星州地质博物馆开发一个新颖的展览，展示生物地质科学的跨学科性质，并强调类似的基本物理化学原理是自然地球化学和地质医学过程的基础。展览将突出上述研究以及我们课题组其他项目的成果。这种方法的优点是它将研究努力与更广泛的教育倡议结合在一起。这个新颖的展览的影响可以从华盛顿大学地质博物馆每年超过25,000名参观者来估计。展览的设计、项目的短期反馈和长期评估、项目的修改和扩展到中西部北部的其他博物馆将与博物馆馆长理查德·斯劳特博士和威斯康星大学的研究、教学和学习一体化中心(CIRTL)合作进行，CIRTL是一个由NSF资助的新的学习和教学中心。博士后助理、研究生和本科生参与拟议工作的所有方面，将为未来的自然科学学术工作者提供研究和外展培训。

AbstractThe investigator's overall career vision is to develop a research program exploring mineral surface interactions with biological macromolecules in processes that are relevant to biogeochemistry (including environmental chemistry, biomineralization and geomedicine), integrated with an educational initiative that (i) increases the public 's awareness of the impact of biogeosciences in their lives,(ii)illustrates how the core physical sciences provide a language for interpreting natural phenomena whether in the external environment or within the human body, and (iii)increases participation of minorities and women in the physical sciences. One major segment of the career plan is described in the present proposal.The research component is to investigate the unique adsorption and self-assembly of phospholipids at the surface of quartz compared to other oxides. The study is motivated by the observation that quartz ruptures cell membranes, composed primarily of phospholipids, whereas amorphous silica, octahedral crystalline silica (stishovite) and other oxides such as corundum and anatase are relatively benign. No satisfactory model currently exits to explain the different biological activity of the mineral phases.Preliminary thermodynamic modeling suggests that the different bioactivity of oxides is due to differences in crystallography and chemical composition as reflected in oxide surface charge and hydration (hydrophilicity) compared to the hydration of the phospholipids. Differences in surface charge and hydration ultimately affect phospholipid adsorption, self-assembly, and extent of organization or rupture. A major objective of the proposed work is to test this hypothesis using a combination of ab initio calculations and collaborative experimental work.Results could have implications for understanding cellularization in the early stages of the evolution of life, cell adhesion to mineral surfaces, the effect of inhaled dusts on cells in the lung, designing biocompatible medical devices, and industrial applications such as the biobeneficiation of ores during processing.Adsorption and self-assembly of phosphatidylcholine from aqueous solution onto the surfaces of quartz, silica glass, orthoclase and anatase will be studied. The effects of pH and background electrolyte will also be examined. Isotherms and microcalorimetry will provide adsorption energies. These experiments will be performed in collaboration with Prof. Anant Menon and Prof. Thomas Record, Department of Biochemistry, University of Wisconsin-Madison (UW). Attenuated Total Reflectance-Fourier Transform Infra-Red spectroscopy (ATR-FTIR) spectroscopy combined with quantum chemical cluster calculations of energies and vibrational frequencies will indicate which specific functional groups of the phospholipids interact with the mineral surface. Morphological changes in the phospholipid self-assembled surface aggregates, which reflect changes in interfacial solvation, will be monitored using Atomic ForceMicroscopy. Vibrational spectroscopy and AFM experiments will be accomplished in collaboration with Prof. Robert Hamers, Department of Chemistry, UW.As part of the career-long educational initiative, during the period of this project, the P.I. and her research group will develop a novel exhibit at the Geology Museum, UW, that demonstrates the interdisciplinary nature of the biogeosciences, and emphasizes the concept that similar fundamental physico-chemical principles underlie natural geochemical and geomedical processes. The exhibit will highlight results from the research proposed above, and from other projects of our research group.The strength of this approach is that it integrates the research efforts with the broader educational initiative. The impact of this novel exhibit may be estimated from the greater than 25,000 visitors annually to the Geology Museum at UW. Design of the exhibit, short-term feedback and long-term evaluation of the project, its modification, and expansion to other museums in the upper Mid-West will be conducted in collaboration with the Museum Director, Dr. Richard Slaughter and UW's Centre for the Integration ofResearch, Teaching and Learning (CIRTL), a new NSF funded Centre for Learning and Teaching.The involvement of a post-doctoral associate, graduate and undergraduate students in all aspects of the proposed work will provide both research and outreach training to the future academic workforce in the physical sciences.