CAREER: Mineral Surface Mediated Organization of Biological Macromolecules

摘要本研究人员的整体职业愿景是发展一项研究计划，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。与一项教育倡议相结合，(i)提高公众对生物地球科学对其生活影响的认识，（ii）说明核心物理科学如何为解释外部环境或人体内部的自然现象提供一种语言，以及（iii）增加少数民族和妇女对物理科学的参与。本建议叙述了职业规划的一个主要部分。研究内容是研究磷脂相对于其他氧化物在石英表面的独特吸附和自组装。这项研究的动机是观察到石英会破坏主要由磷脂组成的细胞膜，而无晶态二氧化硅、八面体结晶二氧化硅（辉石）和其他氧化物如刚玉和锐钛矿则相对无害。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。初步的热力学模型表明，氧化物的不同生物活性是由于晶体学和化学成分的不同，这反映在氧化物的表面电荷和水合性（亲水性）上，而不是磷脂的水合性。表面电荷和水合作用的差异最终影响磷脂的吸附、自组装以及组织或破裂的程度。提出的工作的一个主要目标是使用从头计算和协作实验工作的结合来检验这一假设。研究结果可能对理解生命进化早期阶段的细胞化、细胞与矿物表面的粘附、吸入粉尘对肺部细胞的影响、设计生物相容性医疗设备以及诸如矿石加工过程中的生物净化等工业应用具有重要意义。将研究水溶液中磷脂酰胆碱在石英、硅玻璃、正长石和锐钛矿表面的吸附和自组装。pH值和背景电解质的影响也将被检查。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生物化学系的Anant Menon教授和Thomas Record教授合作进行。衰减全反射-傅立叶变换红外光谱（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华盛顿大学化学系Robert Hamers教授合作完成。作为终身教育计划的一部分，在这个项目期间，P.I.和她的研究小组将在华盛顿大学地质博物馆举办一个新颖的展览，展示生物地球科学的跨学科性质，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的成果，以及我们研究小组的其他项目。这种方法的优势在于它将研究工作与更广泛的教育活动结合起来。这个新展览的影响可以从每年超过25,000名游客到华盛顿大学地质博物馆来估计。展览的设计，项目的短期反馈和长期评估，其修改，以及扩展到中西部上游的其他博物馆，将与博物馆馆长Richard Slaughter博士和华盛顿大学的研究，教学和学习整合中心（CIRTL）合作进行，CIRTL是一个新的NSF资助的学习和教学中心。博士后助理、研究生和本科生参与拟议工作的各个方面，将为未来的物理科学学术劳动力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.