RUI: DNA and nanoparticle assemblies as biomimetic templates for calcium phosphate mineralization

本提案的目的是支持和指导从事生物材料，矿化和仿生学研究的本科生，重点是无机材料化学和生物化学之间的界面分析。这里提出的所有研究都将由一所文科院校的理科本科生完成，该院校有培养女科学家的记录。主要重点将放在指导和培训本科生进入研究的第一年和第二年，并确保这些学生为更大的科学界做出贡献并融入其中。研究学生将接受多种仪器方法（QCM，光学和电子显微镜，AFM， FT-IR等），材料合成（纳米粒子合成，DNA折纸设计和合成）和一般研究方法的培训。这将扩大他们进入行业劳动力或研究生学习的机会。该提案将对伊曼纽尔学院科学和教育部门的可持续研究和基础设施产生积极影响，因为该项目的跨学科性质，并鼓励教师和在校研究生之间的合作。这项研究的结果将通过当地和全国会议的演讲和同行评审的出版物在校园内外提供。这项工作将通过在整个夏季参与和培训高中教师的研究目标以及在学年期间访问高中教师的课堂来影响高中STEM教育。随着PI致力于消除科学与社会之间存在的障碍，夏季的工作将继续影响大学社区。学院社区的成员，包括学生、教师和工作人员将被邀请参观实验室，并在最基础的水平上与本科生研究人员一起进行指导探究实验。总的来说，这项研究和活动对本科生具有变革潜力，并将发展我们对矿化过程的理解和控制。技术摘要：本提案的目的是支持和指导从事生物材料，矿化和仿生研究的本科生，重点是无机材料化学和生物化学之间的界面分析。这种界面的一个例子是磷酸钙离子固体与胶原蛋白和非胶原蛋白在成骨和病理性矿化中的相互作用。在骨和牙外伤和病理性矿化的普遍存在以及缺乏有效的恢复性医疗程序的情况下，显然需要继续研究这一界面。在化学和生物相关系统中，对磷酸钙矿化途径的改进分析，以及可以增强或抑制矿化的新分子和结构的引入，将有助于改善这一需求。具体而言，本研究旨在1)利用先前选择的DNA适体、金纳米粒子和DNA折纸技术，利用多价性、可编程性和表面/溶液通用性，创建和表征仿生DNA和纳米粒子分层组装；2)分析动态、实时、生物相关的胶原矿化系统中的组装结构，该系统集成了微流体溶液控制和定量质量传感。该项目可能产生新的适配体/纳米颗粒组装材料，磷酸钙生物矿化的新模板，以及生物化学和生物工程的新分析工具。这些结果将有助于矿化跨学科领域描述新的分析评价技术，并将矿化与DNA纳米技术的多功能性和可编程性联系起来。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

NON-TECHNICAL ABSTRACTThe purpose of this proposal is to support and mentor undergraduate students pursuing research in biomaterials, mineralization, and biomimetics with an emphasis on analysis at the interface between inorganic materials chemistry and biochemistry. All research proposed here will be completed by undergraduate science students at a liberal arts institution with a record of training women scientists. Primary focus will be on mentoring and training undergraduate students entering research in their first and second year and on ensuring that these students contribute to and integrate with the larger scientific community. Research students will be trained in numerous instrumental methods (QCM, optical and electron microscopy, AFM, FT-IR, and others), materials synthesis (nanoparticle synthesis, DNA origami design and synthesis), and general research methods. This will broaden their opportunities to enter the industry workforce or graduate studies. The proposal will have a positive impact on sustainable research and infrastructure of the science and education departments at Emmanuel College due to the cross-disciplinary nature of the project and by encouraging collaboration between faculty and research students on campus. Findings from this research will be made available on campus and off campus through local and national conference presentations and peer-reviewed publication. This work will impact high school STEM education by engaging and training a high school teacher in the research aims throughout the summer and by visiting the high school teacher's classroom during the school year. Work in the summer will carry forward to impact the college community as the PI works to remove barriers that exist between science and society. Members of the college community, including students, faculty, and staff will be invited to visit the lab and join undergraduate student researchers in a guided inquiry experiment at the most basic level. Collectively, this research and activities have transformative potential for undergraduate students and will develop our understanding and control of the mineralization process.TECHNICAL ABSTRACTThe purpose of this proposal is to support and mentor undergraduate students pursuing research in biomaterials, mineralization, and biomimetics with an emphasis on analysis at the interface between inorganic materials chemistry and biochemistry. An example of this interface is in the interaction between calcium phosphate ionic solids with collagenous and non-collagenous proteins in bone osteogenesis and in pathological mineralization. The need for continued study of this interface is apparent in the prevalence of bone and dental trauma and pathological mineralization and in the lack of effective restorative medical procedures. Improved analysis of the calcium phosphate mineralization pathways, in chemically- and biologically-relevant systems, and the introduction of new molecules and structures that can enhance or inhibit mineralization will help to ameliorate this need. Specifically, this research aims to 1) create and characterize biomimetic DNA and nanoparticle hierarchical assemblies, using previously selected DNA aptamers, gold nanoparticles, and DNA origami technology, to take advantage of multi-valency, programmability, and surface/solution versatility; and 2) analyze assembled structures in dynamic, real-time, biologically-relevant collagen mineralization systems that integrate microfluidic solution control and quantitative mass sensing. This project may yield the creation of new aptamer/nanoparticle assembled materials, new templates for calcium phosphate biomineralization, and new analysis tools for biochemistry and bioengineering. These results will be beneficial to the interdisciplinary field of mineralization in describing new analytical evaluation techniques and in connecting mineralization with the versatility and programmability of DNA nanotechnology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.