RUI: Charge Modified Antibody for Robust and Directional Adsorption onto Gold Nanoparticles

为了防止生物威胁和开发有效的药物疗法，需要开发新的检测战略。金纳米颗粒(AuNPs)的独特性质使其成为检测技术中的候选材料。新出现的检测技术成功的关键是将蛋白质，即抗体附着到AuNPs的表面。尽管在抗体-AuNP结合化学领域进行了广泛的努力，但目前的结合化学并不是普遍适用于所有抗体，往往会削弱抗体的功能，并导致化合物的稳定性有限。为了应对这些挑战并实现AuNP检测的全部潜力，Jeremy Driskell博士和他在伊利诺伊州立大学的研究小组正在研究抗体-AuNP相互作用的基本原理。这项研究是在大分子、超分子和纳米化学计划的支持下进行的。这些研究将促进高活性和稳定的抗体-AuNP结合物的合理设计。该项目为学习高级分析技术并欣赏多学科方法解决问题的本科生提供了密集的研究体验。此外，Driskell博士和他的本科生还参加了伊利诺伊州夏季研究学院，这是一个教育推广项目，为来自全国各地的高中生提供在研究实验室工作的机会。尽管有许多成功的抗体-AuNP偶联物的例子，但固定化化学仍然是一个挑战。抗体在AuNPs上的直接吸附通常是有效的；然而，不同蛋白质的吸附条件以一种不可预测的方式变化，结合物的活性也是不同的。Driskell博士的研究试图找出导致某些抗体吸附到AuNPs上形成稳定的、高活性的结合物的潜在原理，而其他抗体吸附较弱和/或结合活性较差。Driskell博士的实验室通过测量抗体在AuNPs上的吸附亲和力、取向、可逆性和与其他蛋白质的置换来研究抗体在AuNPs上的吸附动力学。抗体经过化学修饰，可以精确地改变蛋白质的电荷。对吸附的系统研究阐明了建立有效表面修饰预测模型所需的基本原理。这些努力支持了Driskell博士的长期目标，即开发一种战略，将抗体固定在AuNP上，形成高度活性、定向和稳定的结合物，用于AuNP启用的免疫分析。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The need to protect against biological threats and to develop effective drug therapies requires the development of novel detection strategies. The unique properties of gold nanoparticles (AuNPs) make them candidates for materials used in detection technologies. Critical for the success of emerging detection technologies is the attachment of proteins, i.e., antibodies, onto the surface of the AuNPs. Despite extensive efforts in the area of antibody-AuNP conjugation chemistry, current attachment chemistries are not universally applicable to all antibodies, often diminish the function of the antibody, and result in compounds with limited stability. In an effort to address these challenges and to realize the full potential of AuNP-enabled assays, Dr. Jeremy Driskell and his research group at Illinois State University are investigating the underlying principles of the antibody-AuNP interaction. This research is conducted with the support of the Macromolecular, Supramolecular and Nanochemistry Program. These studies will promote the rational design of highly active and stable antibody-AuNP conjugates. The project provides an intense research experience to undergraduate students who learn advanced analytical techniques and gain an appreciation for a multidisciplinary approach to problem solving. Additionally, Dr. Driskell and his undergraduate students participate in the Illinois Summer Research Academy, an educational outreach program that provides high school students from across the nation with an opportunity to work in a research laboratory. Despite many successful examples of antibody-AuNP conjugates, immobilization chemistry still presents a challenge. Direct adsorption of the antibody onto AuNPs is often effective; however, adsorption conditions vary among proteins in an unpredictable manner and the activity of the conjugate is variable. Dr. Driskell's research seeks to identify the underlying principles that cause some antibodies to adsorb onto AuNPs to form stable, highly active conjugates, while other antibodies adsorb weakly and/or exhibit poor binding activity. Dr. Driskell's lab investigates the adsorption dynamics of antibodies onto AuNPs by measuring the adsorption affinity, orientation, reversibility, and displacement by other proteins. Antibodies are chemically modified to precisely alter the protein charge. A systematic investigation into adsorption elucidates the foundational principles needed to build a predictive model for effective surface modification. These efforts support Dr. Driskell's long-term goal of developing a strategy to immobilize antibodies onto AuNPs to form highly active, oriented, and stable conjugates for use in AuNP-enabled immunoassays.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.