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

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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.