Scanning probe force microscopy to study biophysics of lipid rafts and their role in amyloid fibril formation

生命系统的几乎每一项功能都涉及由膜隔开的隔间之间的物质或信号的协调和调节交换。质膜本身是由小的动态隔室--筏组成的。这些木筏是细胞交流的中心。由于它们的重要作用，迅速增加的疾病清单被认为与木筏有关也就不足为奇了。这些疾病包括阿尔茨海默氏症和帕金森氏症，仅举几例。因此，对脂筏的性质和功能的详细研究对于理解重要的生物学过程的分子机制和淀粉样蛋白相关疾病的发生具有重要意义。本项目的目的是研究静电相互作用，由于脂筏中不均匀的表面电荷分布，静电相互作用可能在纤维形成的起始和有效性中发挥重要作用。由于木筏的小(纳米)尺寸，研究它们是一项要求非常高的工作，需要非常先进的显微技术。我们将结合原子力显微镜(AFM)和环境中的局部表面电位测量来研究它们的结构和静电相互作用。我们将使用德累斯顿技术大学最近开发的最先进的开尔文探针力显微镜的改进，它允许在真空和空气中进行高分辨率表面电势测量，并有望在液体中应用。这项技术将被用于商业NanoWizardAFM显微镜，开尔文技术将进一步发展，用于在液体环境中操作。这将推进开尔文探针力显微镜技术本身，该技术目前分辨率较低，仅限于在真空和空气中操作，并将提供对脂筏在淀粉样纤维形成中的作用的洞察。

Almost every function of a living system involves a coordinated and regulated exchange of matter or signals between compartments separated by membranes. Plasma membrane itself is composed of small dynamic compartments - rafts. These rafts are central to the communication of cells. Because of their essential role, it is not surprising that rapidly growing list of diseases is thought to be related to rafts. These include Alzheimer's and Parkinson's diseases, to list a few. Therefore detailed studies of the lipid rafts' nature and functions are important for the understanding of the molecular mechanisms of biologically important processes and initiation of amyloid related diseases. The goal of this project is to investigate the electrostatic interactions, which due to the nonuniform surface charge distribution in lipid rafts may play an important role in the initiation and effectiveness of fibril formation. Because of the rafts' small (nanometer) size, studying them is a demanding undertaking requiring highly advanced microscopic techniques. We will combine atomic force microscopy (AFM) with the local surface potential measurements in an ambient environment to address both their structure and the electrostatic interactions. We will use the most advanced modification of Kelvin probe force microscopy recently developed in Dresden Technical University, which permits high resolution surface potential measurements in vacuum and in air, and is promising for applications in liquid. This technology will be adapted to a commercial NanoWizardAFM microscope and the Kelvin technique will be further developed for operating in a liquid environment. This will advance the Kelvin probe force microscopy technique itself, which currently has low resolution and is restricted to operating in vacuum and air, as well as will provide an insight into the role of lipid rafts in amyloidal fibril formation.