IDR: Coupling Theory and Experiment to Quantify Biomolecule-Nanomaterial Interactions

该奖项的研究目标是开发测量方法和解释生物分子(如蛋白质和DNA)与精细或纳米材料之间的相互作用的理论模型。这些知识将是发展科学和工程基础的基础，无论是设计使用生物分子-纳米材料杂化的疗法，还是理解纳米材料对健康可能的有害影响。所采取的方法将是开发和使用实验和理论上的补充工具。该项目首先将重点放在定义明确的核酸-碳纳米管系统上，并将(I)测量将单个生物分子从单个纳米颗粒中分离出来所需的力，(Ii)开发理论模型，将原始实验测量结果转化为基本物理性质，以及(Iii)在模拟细胞环境中研究生物分子与纳米颗粒之间的结合和竞争。如果成功，这项研究的好处将是产生基本的定量数据，揭示支配生物分子和纳米材料之间相互作用的基本原理，并提出通过化学修饰操纵它们的方法。这些信息对于使用新的混合结构的新疗法的设计至关重要。例如，定量了解治疗性生物分子和碳纳米管之间的结合强度将允许设计依赖于药物输送的疗法，使用这种纳米材料作为载体。同样，这项研究的结果将有助于开发框架，以了解纳米材料与人类细胞中生物分子之间的基本相互作用，并预测潜在的有害影响。该奖项还将通过与当地一家科学博物馆的合作，支持为普通公众开展关于纳米材料对健康影响的机械基础及其在生物医学中的潜在应用的非正式科学教育。

The research objective of this award is to develop methods to measure, and theoretical models to interpret, the interaction between biological molecules, such as proteins and DNA, and fine-scale or nano-materials. This knowledge will be fundamental for the development of the scientific and engineering basis, both for the design of therapies that employ biomolecule-nanomaterial hybrids, and for understanding of the possible deleterious effects of nanomaterials on health. The approach taken will be to develop and employ complementary tools in experiment and theory. The project will initially focus on the well-defined nucleic acid-carbon nanotube system and will (i) measure forces required to detach single biological molecules from individual nanoparticles, (ii) develop theoretical models to convert raw experimental measurements into fundamental physical properties, and (iii) study binding and competition between biomolecules and nanoparticles in a simulated cellular environment. If successful, the benefits of this research will be to generate fundamental quantitative data, to uncover underlying principles that govern the interaction between biological molecules and nanomaterials, and to suggest ways to manipulate them through chemical modifications. Such information is critical for the design of novel therapies using new hybrid constructs. For example, knowing quantitatively the strength of binding between a therapeutic biological molecule and a carbon nanotube will permit the design of therapies that rely on the delivery of the drug using this nanomaterial as a carrier. Similarly, the results of this research will help to develop the framework for understanding the basic interactions between nanomaterials and the biological molecules in human cells and for predicting potentially harmful effects. This award will also support, through collaboration with a local science museum, the development of informal science education for the general public about the mechanistic basis of the health effects of nanomaterials and their potential applications in biomedicine.