UNDERSTANDING THE INTERACTION OF ANKYRINS AND NANOMATERIALS

描述（由申请人提供）：蛋白质与固体表面的相互作用是一种基本现象，涉及纳米技术、生物材料和生物技术过程。虽然“大多数蛋白质与大多数表面相互作用”，但每种相互作用的特定强度、机制和动力学对吸附蛋白质的最终构象有重要影响。吸附的基础通常是由疏水和静电相互作用的某种组合提供的。疏水相互作用通常被认为是驱动结合的有利自由能变化的主要因素，但它会导致吸附蛋白质的重大重排和生物活性损失。静电相互作用，虽然通常太弱而不能提供长期稳定性，但可以保留蛋白质结构，并可以通过多种方式进行控制。因此，我们建议1)利用静电力来控制蛋白质在电极表面的吸附过程；2)通过调节施加在表面的电位来操纵被吸附蛋白质的活性。这个项目的假设是通过控制潜在的应用

DESCRIPTION (provided by applicant): The interaction of proteins with solid surfaces is a fundamental phenomenon with implications on nanotechnology, biomaterials and biotechnological processes. Although "most proteins interact with most surfaces", the particular strength, mechanism, and kinetics of each interaction has significant consequences in the final conformation of the adsorbed protein. The basis for the adsorption is generally provided by some combination of hydrophobic and electrostatic interactions. While generally recognized as the major contributor to the favorable free energy change driving the binding, hydrophobic interactions induce significant rearrangements and losses in biological activity in the adsorbed protein. Electrostatic interactions, though typically too weak to provide long-term stability, enabe preserving the protein structure and can be controlled by a variety of ways. Hence, we propose to 1) exploit electrostatic forces to control the adsorption process of proteins to electrode surfaces and 2) manipulate the activity of the adsorbed proteins by adjusting the potential applied to the surface. The hypothesis of this project is that by controlling the potential applied to the surface (electrode), it will be possible to affect the adsorption process (affinity, mechanism, and kinetics) and most importantly, the biological activity of the adsorbed proteins. Current evidence, though only sparsely reported and mostly qualitatively expressed, supports this hypothesis. Thus, the main goal of this project is to systematically demonstrate that (and understand how, why, and how fast) changes in electrode potential can affect the adsorption, orientation, conformation, activity, and stability of adsorbed proteins. For these studies, we have selected a group of proteins called ankyrins. These proteins display an unusually high stability and fully reversible spring-like behavior. Besides the fact that there are no reports related to adsorption behavior of these proteins, this proposal will determine the fundamental mechanism of surface potential in the adsorption and final conformation, which is crucial to bolster the rational development and application of sensors and nanodevices. Furthermore, understanding how ankyrins and other membrane proteins, interact with nanomaterials will form the basis for the development of a high-throughput model to study a broad range of pathologies linked to defective protein-protein interactions, such as hereditary spherocytosis, spinocerebellar ataxia, cardiac arrhythmias, and a variety of channelopathies. The proposed project will also develop a novel surface-based method to study real-time binding of proteins in the presence of pharmaceutical compounds that would otherwise interfere with the association of other proteins in cells.