Active Control of Biomolecular Interactions using Redox Amphiphiles

智力优势：该项目旨在广泛推进可主动控制的两亲性系统的分子水平设计。该研究主要集中在表面活性剂、阳离子脂质和含有氧化活性基团二茂铁的肽两亲体上，并试图表征和理解这些两亲体自组装的变化，这些变化伴随着二茂铁氧化态的电化学控制变化。该研究的第一个目标是了解发生在电极附近的过程，浸入双尾含二茂铁两亲体的水溶液中。通过使用小角中子散射（SANS）、低温透射电子显微镜（cro - tem）和差示扫描量热法，该项目侧重于(i)这些两亲体的物理化学性质如何影响它们在电极上的氧化速率，（ii）如何使用氧化还原介质来加速这些速率，以及（iii）氧化状态变化后产生的自组装动力学。研究的第二个目标是由研究人员发现，操纵含二茂铁的两亲体的氧化状态可以用来影响DNA向细胞的传递。他们试图通过表征含有两亲体和DNA的二茂铁形成的纳米结构，并使用SANS和低温透射电镜作为两亲体氧化态的函数，来提供对这些观察结果的见解。本提案中描述的第三个研究目标是建立对一类具有寡肽作为头基团的新型生物分子两亲体的主动控制。由于过去的研究表明肽两亲体的生物学功能强烈依赖于它们的自组装，研究人员假设主动控制自组装的原理将为实现生物分子界面功能的时空控制提供新的途径。重点是二茂铁肽两亲体和主动控制这些两亲体自组装成纳米纤维凝胶。更广泛的影响：在溶液中以特定速率和特定位置改变分子的两亲性的能力有可能广泛影响表面活性剂科学，使新型实验成为可能，这些实验将促进我们对表面活性剂系统的动态和平衡特性的理解。例如，表面活性剂在不同两亲性状态之间循环的能力为确定表面活性剂体系的平衡状态提供了新的手段（传统实验中的结论可能是模糊的）。此外，能够改变溶液中分子的两亲性，从而遵循导致新纳米结构的动态过程，为研究复杂表面活性剂体系的动力学过程这一鲜为人知的主题提供了新工具的基础。这项研究所产生的知识的技术潜力也是巨大的。主动控制分子两亲性的能力将使在一系列技术背景下控制基于表面活性剂的现象成为可能，包括分离、药物传递、材料合成和生物分子界面设计（例如，用于蛋白质分析）。本提案中描述的研究还通过结合胶体化学，界面工程（雅培）和生物分子和材料工程（林恩）的项目，为研究生和本科生的教育提供了令人兴奋的机会。这些学生还将有不同寻常的机会参与两个国际合作（与以色列和日本的合作者）。

CBET-0754921AbbottIntellectual Merit: This project seeks to broadly advance the molecular level design of amphiphilic systems that can be controlled actively. The research is focused on surfactants, cationic lipids and peptide amphiphiles that incorporate the redox-active group ferrocene, and seeks to characterize and understand changes in the self-assembly of these amphiphiles that accompany electrochemically controlled changes in the oxidation state of ferrocene. The first goal of the research is to understand processes that occur near electrodes immersed into aqueous solutions of ferrocene-containing amphiphiles with double tails. By using small angle neutron scattering (SANS), cryo-transmission electron microscopy (cryo-TEM) and differential scanning calorimetry, the project focuses on (i) how the physicochemical properties of these amphiphiles influence their rates of oxidation at electrodes, (ii) how redox mediators can be used to accelerate these rates, and (iii) the resulting dynamics of self-assembly that follow changes in oxidation state. The second goal of the research is motivated by the Investigators' discovery that manipulation of the oxidation state of ferrocene-containing amphiphiles can be used to influence the delivery of DNA to cells. They seek to provide insights into these observations by characterizing the nanostructures formed by ferrocene containing amphiphiles and DNA using SANS and cryo TEM as a function of the oxidation state of the amphiphiles. The third goal of research described in this proposal moves to establish active control of a new class of biomolecular amphiphiles that possess oligopeptides as head groups. Because past studies have demonstrated that the biological function of peptide amphiphiles depends strongly on their self-assembly, the investigators hypothesize that principles for active control of self-assembly will provide new avenues for achieving spatial and temporal control of the function of biomolecular interfaces. A focus is directed to ferrocene-containing peptide amphiphiles and active control of the self-assembly of these amphiphiles into nanofiber gels. Broader Impacts: The ability to transform the amphiphilicity of molecules at defined rates and at specified locations in solution has the potential to broadly impact surfactant science by enabling new types of experiments that will advance our understanding of the dynamic and equilibrium properties of surfactant systems. For example, the ability to cycle a surfactant between different amphiphilic states provides new means to determine the equilibrium states of surfactant systems (where conclusions in conventional experiments can be ambiguous). Also, the ability to switch the amphiphilicity of molecules in solution, and thus follow dynamic processes leading to new nanostructures, provides the basis of a new tool to investigate the poorly understood topic of kinetic processes in complex surfactant based systems. The technological potential of the knowledge to be generated by this research is also substantial. The ability to actively control the amphiphilicity of molecules will enable control of surfactant-based phenomena in a range of technological contexts, including separations, drug delivery, materials synthesis, and design of biomolecular interfaces (e.g., for protein assays). The research described in this proposal also provides exciting opportunities for the education of graduate and undergraduate students through projects that combine colloid chemistry, interface engineering (Abbott) and biomolecular and materials engineering (Lynn). These students will also be presented with the unusual opportunity of being involved in two international collaborations (with collaborators in Israel and Japan).