Berest V. Biophysical properties of natural membrane-active peptides

Object of study: mechanisms of the modification of interaction of membrane-active peptides with natural and model lipid membranes. The subject of research is the effect of membrane-active peptides on model phospholipid and cell membranes, as well as their effect on the morphological and functional properties of blood cells and nerve tissue. Objective: to establish molecular mechanisms of modulation of the interaction of membrane-active peptides with model and natural lipid membranes. Research methods: light scattering, microwave dielectrometry, UV spectroscopy, fluorescence spectroscopy, BLM, gel electrophoresis, light microscopy, microfluidics, impedance spectroscopy, flow cytometry, mathematical modeling. Scientific novelty: the replacement of the polar asparagine by serine in the prion peptide promotes aggregation of the peptide in bilayer lipid membranes with the formation of cation-selective pore. Cholesterol attenuates the hemolytic effect of the cyclic oligopeptide GS. Modulation of GS sorption onto model lipid membranes in the presence of cholesterol and D-g-PAA(PE) is governed the binding of GS oligomers to the membrane. Decrease in lipid ordering in the bilayer during gamma irradiation or lipid peroxidation of platelet and erythrocyte membrane leads to easier distribution of gramicidin S into the membrane and at the same time to reduced retention of the peptide in membrane. Single ion channel currents of the reconstituted CLC-like yeast protein were recorded corresponding to potential dependent Cl channel. Practical significance: the possibility modification of the membrane structure to increase their resistance to the lytic action of the antimicrobial peptide GS has been established. The elucidated biophysical mechanisms of GS incorporation into membranes can be used to create peptide analogues and delivery vehicles of membranotropic drugs. The established inhibition of platelet aggregation by peptide can be used for the development of topical anticoagulants.