CAREER: Understanding Nanoparticle-induced Changes to Protein Structure

在化学系化学结构、动力学和机制A（CSDM-A）项目的支持下，范德比尔特大学的劳伦·布坎南正在开发能够使用先进的光谱方法测量纳米颗粒引起的蛋白质结构变化的方法。了解这些变化需要一种实验方法，能够观察纳米颗粒结合蛋白质的高结构分辨率，由于样品的异质性和广泛的，重叠的光谱特征的技术挑战。布坎南博士和她的学生将结合联合收割机二维红外光谱和同位素标记，以提供深入了解蛋白质纳米材料相互作用的结构和动力学。总之，这些技术允许将结构变化定位于蛋白质内的单个残基。通过这项调查的发现，预计将提高纳米粒子暴露对生物系统的影响的理解，并促进生物纳米共轭材料在化学，生物学和材料科学中的应用设计。研究生和本科生都积极参与使用先进光谱技术的生物物理化学研究。Buchanan博士还负责监督《青年科学家》，这是一本面向高中生的研究期刊。根据该奖项，正在使用二维红外光谱研究纳米颗粒组成，大小和组成对肽和蛋白质二级结构的作用。为了达到这种分辨率水平，也采用了特定位点的振动探针。在这样做时，光谱拥塞将被减少，从而可以探索与纳米颗粒对肽自组装的抑制或加速如何影响聚集体的结构组织和热力学稳定性有关的问题。Buchanan博士和她的团队将确定纳米颗粒如何改变聚集途径，特别关注确定是否形成新的中间物种或结构多晶型物。有助于更好地理解蛋白质-纳米颗粒相互作用的方法在未来可以被广泛应用，以更好地解释生物和合成聚合物自组装成分层结构。该奖项反映了NSF的法定使命，并被认为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来支持。

With support from the Chemical Structure, Dynamics, and Mechanisms A (CSDM-A) Program in the Division of Chemistry, Lauren Buchanan of Vanderbilt University is developing methods capable of measuring nanoparticle-induced changes to protein structure using advanced spectroscopic methods. Understanding these changes requires an experimental approach capable of observing nanoparticle-bound proteins with high structural resolution, a technological challenge due to sample heterogeneity and broad, overlapping spectral features. Dr. Buchanan and her students will combine two-dimensional infrared spectroscopy and isotopic labeling to provide insight into both the structure and dynamics of protein-nanomaterial interactions. Together, these techniques allow structural changes to be localized to individual residues within proteins. Discoveries made through this investigation are expected to improve understanding of the effects of nanoparticle exposure on biological systems and facilitate the design of bio-nano conjugated materials for applications in chemistry, biology, and materials science. Both graduate and undergraduate students actively participate in this biophysical chemistry research using advanced spectroscopic techniques. Dr. Buchanan also oversees “Young Scientist”, a research journal for high school students. Under this award, the role of nanoparticle composition, size, and composition on the secondary structure of peptides and proteins is being studied using two-dimensional infrared spectroscopy. To achieve this level of resolution, site-specific vibrational probes are also being employed. In so doing, spectral congestion will be reduced so that questions related to how inhibition or acceleration of peptide self-assembly by nanoparticles affects the structural organization and thermodynamic stability of the aggregates can be explored. Dr. Buchanan and her group will determine how nanoparticles alter aggregation pathways, with particular focus on determining whether new intermediate species or structural polymorphs are formed. Methods that facilitate better understanding of protein-nanoparticle interactions could be broadly applied in the future to better explain self-assembly of both biological and synthetic polymers into hierarchical structures.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.