Growth behavior of Aβ protofibrils on liposome membranes and their membrane perturbation effect

The protofibrils of amyloid fibrils have recently drawn an attention due to their cytotoxicity although the physicochemical properties of the protofibrils as an intermediate of fibrillation process have still remained unclear. We investigated the growth behavior of the protofibrils of amyloid β protein with 40 amino acid residues in the presence of various liposomes and the membrane perturbation (calcein leakage). The growth behavior of protofibrils was apparently correlated with the protofibrils-induced calcein leakage. From the binding experiment using a hydrophobic fluorescence probe and the quartz crystal microbalance method combined with the planar lipid membrane, it is suggested that the apparent correlation between the growth behavior of protofibrils and their membrane perturbation resulted from the physicochemical properties of protofibrils such as hydrophobicity and the stability of hydrogen bonds. The protofibrils were found to show the highest hydrophobicity and the highest instability of hydrogen bonds of the proteins used in this study (monomer, protofibrils, matured fibrils, and other three typical proteins). It is anticipated that such properties of protofibrils were advantageous both for the binding of protofibrils with monomer (growth behavior) and for the binding of lipid bilayer membranes (membrane perturbation).