Nanoscale Electrostatic Domains Induced by Cholesterol in Model Lipid Membranes Relate to Amyloid Binding and Toxicity

Kelvin Probe Force Microscopy (KPFM) is a type of scanning probe microscopy which specifically addresses electrostatic properties of materials and has a great potential to bring new discoveries in biomedical research, but currently has limited biological applications.In this work, we report one of a very few applications of Kelvin probe force microscopy (KPFM) to study complex structures of lipid films and lipid-protein interactions. Molecular arrangement of lipids and proteins gives rise to complex film morphology as well as distinct electrical surface potentials, which may rule many biological processes and diseases. Using Frequency Modulated - KPFM (FM-KPFM) we discovered an intriguing nanoscale electrostatic effect of cholesterol that may be crucial for understanding the mechanism of amyloid toxicity in relation to Alzheimer's disease (1). Earlier we observed similar electrostatic domains induced by cholesterol in pulmonary surfactant (2,3). Here we show that this electrostatic effect of cholesterol is not specific to only pulmonary surfactant films, but is also present in model lipid systems and plays an important role in amyloid-lipid interactions. We postulate that this previously unknown nanoscale electrostatic effect of cholesterol is a fundamental property, which may greatly influence the interactions of lipid membranes with other charged molecules.1. E.Drolle, R.M.Gaikwad, Z.Leonenko, Nanoscale electrostatic domains in cholesterol-laden lipid membranes create a target for amyloid binding. Biophysical Journal, Letters, 2012, 103(4), L27-L292. E.Finot, Y.Leonenko, B.Moores, L.M.Eng, M.Amrein, Z.Leonenko. Effect of cholesterol on electrostatics in lipid-protein films of a lung surfactant, Langmuir, 2010, 26 (3), 1929-1935.3. B.Moores, F.Hane, L.M.Eng, Z.Leonenko, Kelvin probe force microscopy in application to biomolecular films: Frequency modulation, amplitude modulation, and lift mode, Ultramicroscopy, 2010, 110(6), 708-711.