Active Control of Biomolecular Interactions using Redox Amphiphiles

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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).