Biophysical study of nanoscale structure and properties of lipid membrane and fundamental mechanisms of interactions of lipid membrane with antimicrobial and amyloid peptides

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Amyloid fibrils are insoluble protein aggregates which are associated with multiple neurodegenerative disorders, such as Alzheimer's disease. The molecular mechanism of amyloid toxicity is currently not well understood and requires a detailed understanding of the interactions of amyloid peptides with biomembrane. The biomembrane structure is complex and nonuniform as it is composed of small dynamic compartments called rafts. The detailed studies of the lipid rafts' nature and functions are important for the understanding of the molecular mechanisms of amyloid peptide binding to the membrane and their toxicity. I propose to investigate the similarities and differences between amyloid and antimicrobial peptides in order to understand the mechanism of their electrostatic interactions with lipid membranes. We will pay specific attention to the effect of lipid composition and cholesterol which induce raft formation and change electrostatic heterogeneity in the lipid membrane. We will combine atomic force microscopy (AFM) with the local surface potential measurements with the use of the most advanced modification of Kelvin probe force microscopy. In addition a combined AFM-patch clamp set up will be built to allow simultaneous AFM imaging and nanoscale electrical recording on a lipid membrane. These advanced scanning probe methods will allow us to investigate the nanoscale structure and physical properties of lipid membranes in order to understand how they may control membrane interactions with these peptides. The proposed research program will advance knowledge in the areas of membrane biophysics, as well as membrane-peptide interactions and will provide an insight into the role of lipid rafts in amyloidal and antimicrobial peptides action. This may promote the development of novel biomedical applications in relation to antimicrobial drug resistance or amyloid toxicity. In addition, the program will provide excellent interdisciplinary training for multiple students and researchers involved in this program.