Active Control of Biomolecular Interactions using Redox Amphiphiles

使用氧化还原两亲物主动控制生物分子相互作用

• 批准号: 0754921
• 负责人: Nicholas Abbott
• 金额: $ 30万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0754921&HistoricalAwards=false
• 关键词: Active; Control; Biomolecular; Interactions; using

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).

CBET-0754921 AbbottIntellectual Merit：该项目旨在广泛推进可主动控制的两亲系统的分子水平设计。该研究的重点是表面活性剂，阳离子脂质和肽两亲物，将氧化还原活性基团二茂铁，并试图表征和了解这些两亲物的自组装伴随电化学控制的变化在二茂铁的氧化态的变化。这项研究的第一个目标是了解浸入含二茂铁的双尾两亲物水溶液中的电极附近发生的过程。通过使用小角中子散射（SANS），低温透射电子显微镜（cryo-TEM）和差示扫描量热法，该项目的重点是（i）这些两亲物的物理化学性质如何影响它们在电极上的氧化速率，（ii）氧化还原介体如何用于加速这些速率，以及（iii）氧化态变化后自组装的动力学。该研究的第二个目标是由研究人员发现的，即操纵含二茂铁的两亲物的氧化态可用于影响DNA向细胞的递送。他们试图通过使用SANS和cryo TEM表征由含有两亲物的二茂铁和DNA形成的纳米结构作为两亲物的氧化态的函数来提供对这些观察的见解。本提案中描述的研究的第三个目标是建立对一类新的生物分子两亲物的主动控制，这些生物分子两亲物具有寡肽作为头部基团。由于过去的研究表明，肽两亲物的生物功能强烈依赖于它们的自组装，研究人员假设，自组装的主动控制原则将为实现生物分子界面功能的空间和时间控制提供新的途径。一个焦点是针对含二茂铁的肽两亲物和主动控制这些两亲物的自组装成凝胶。更广泛的影响：以规定的速率和在溶液中的指定位置转换分子的两亲性的能力，有可能通过使新型实验，将推进我们对表面活性剂系统的动态和平衡性质的理解，广泛影响表面活性剂科学。例如，使表面活性剂在不同的两亲性状态之间循环的能力提供了确定表面活性剂体系的平衡状态的新手段（其中常规实验中的结论可能是模糊的）。此外，在溶液中切换分子的两亲性的能力，从而遵循导致新的纳米结构的动态过程，提供了一个新的工具来研究在复杂的表面活性剂为基础的系统中的动力学过程的知之甚少的主题的基础。这项研究所产生的知识的技术潜力也很大。主动控制分子的两亲性的能力将使得能够在一系列技术背景下控制基于表面活性剂的现象，包括分离、药物递送、材料合成和生物分子界面的设计（例如，用于蛋白质测定）。本提案中描述的研究还通过结合联合收割机胶体化学、界面工程（Abbott）和生物分子与材料工程（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。这些学生还将获得参与两项国际合作（与以色列和日本的合作者）的难得机会。