Elucidating Bio-Nano Interface Atomic Structure and Peptide Directed Nanoparticle Formation

圣地亚哥州立大学的Gregory Holland在化学系的大分子、超分子和纳米化学项目的支持下，正在开发纳米生物界面的原子和分子水平的结构理解，以及纳米颗粒曲率、介孔性和形态对生物分子配体结构、动力学和纳米颗粒表面组织的影响。无机核和生物分子配体涂层是结构上不同的实体，但强烈地相互影响，协同地确定纳米颗粒系统的集体性质。感兴趣的系统包括一系列具有不同形态的二氧化硅纳米结构和用蛋白质和脂质基配体官能化的自然灵感的羟基磷灰石纳米材料。阐明生物分子在纳米材料上组装的原子、分子和纳米尺度的细节，开发新型的肽导向纳米颗粒合成和理解生物分子在纳米颗粒上的表面化学是研究的重点。这些基本的化学知识可能有助于开发下一代将纳米材料与生物分子功能相结合的设备和传感器。该项目正在为各级学生创造宝贵的研究培训机会，并进一步与外联活动的发展相结合。霍兰德博士正在建立一个高度跨学科的研究和教育计划的纳米粒子表面表征涉及研究生，本科生和高中实习生的广泛参与，有助于培训多样化的劳动力。绝大多数化学合成和天然存在的纳米结构，无论其化学成分，无机核，形态和结晶度，都被配体壳包覆。本研究的主要目标是确定纳米生物界面的原子和分子水平结构，并利用生物分子，包括肽和脂质作为纳米颗粒合成策略中的配体。有两个主要焦点：（1）研究组装在一系列纳米结构二氧化硅上的生物分子，包括胶体单分散球、高度缺陷的支化气相二氧化硅和中孔二氧化硅纳米颗粒，其中关注封装在纳米孔内的生物分子的行为;和（2）用肽作为模板剂合成的自然激发的羟基磷灰石纳米棒和纳米片。物理/分析技术的组合将用于研究，包括固态NMR光谱，电子显微镜和分子动力学模拟（MDS），以确定这些系统界面处肽和脂质的结构和组装，并阐明纳米颗粒曲率和形态对配体结构的影响。这项工作是扩大的合成和表征方法提供给全球纳米科学界提高纳米生物结构的基本理解。这一奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Gregory Holland of San Diego State University is developing atomic and molecular level structural understanding of nano-bio interfaces and the influence of nanoparticle curvature, mesoporosity and morphology on biomolecular ligand structure, dynamics and organization on nanoparticle surfaces. The inorganic cores and the biomolecular ligand coatings are structurally distinct entities but strongly influence each other synergistically determining the collective properties of the nanoparticle system. The systems of interest include a range of silica nanostructures with varying morphology and naturally inspired hydroxyapatite nanomaterials functionalized with protein- and lipid-based ligands. Elucidating the atomic, molecular and nanoscale detail of biomolecular assembly on nanomaterials, developing novel peptide-directed nanoparticle syntheses and understanding the surface chemistry of biomolecules on nanoparticles is the research focus. This fundamental chemical knowledge could contribute to the development of next generation devices and sensors that couple nanomaterials with biomolecular functionality. The project is creating valuable research training opportunities for students at various levels that is further integrated with outreach activity development. Dr. Holland is building a highly interdisciplinary research and education program on nanoparticle surface characterization involving broad participation of graduate, undergraduate and High School interns contributing to the training of a diverse workforce.The vast majority of chemically synthesized and naturally occurring nanostructures, regardless of their chemical compositions, inorganic core, morphology and crystallinity, are coated with a ligand shell. The primary goal of this research is to determine the atomic and molecular level structure of nano-bio interfaces and to exploit biomolecules, including peptides and lipids as ligands in nanoparticle synthetic strategies. There are two main foci: (1) to investigate biomolecules assembled on a range of nanostructured silicas including colloidal monodisperse spheres, highly defective, branched fumed silica, and mesoporous silica nanoparticles where the behavior of biomolecules encapsulated within nanopores is the focus; and (2) naturally inspired hydroxyapatite nanorods and nanosheets synthesized with peptides as the templating agents. A combination of physical/analytical techniques will be used in the research, including solid-state NMR spectroscopy, electron microscopy and molecular dynamics simulation (MDS) to determine the structure and assembly of peptides and lipids at the interface of these systems and elucidate the influence of nanoparticle curvature and morphology on ligand architecture. This work is expanding on the synthetic and characterization methods available to the global nanoscience community for improved fundamental understanding of nano-biostructures.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.