The Effect Of Interfacial Property On The Aggregation And Fibrosis Of A? Peptide

Alzheimer's Disease(AD)is a neurodegenerative disease characterized by learning,memory and cognitive impairment.The main pathological feature of AD is amyloid ?(A?peptide)aggregates in cerebral cortex and formed fibril-shaped amyloid plaques.The reason for A? peptide fibril forming is A? peptide transforming to a kind of aggregates,which is insoluble with ?-sheet structure originating from soluble single-chain molecular with random coil structure.The dynamic diffusion of A? peptide on 2D-interface determined the growth process of A? peptide on several interfaces.In addition,the dynamic diffusion of A? peptide molecule is related to the physicochemical properties of surface,therefore,the interaction between A? peptide and different surfaces are diversely.At present,restraining aggregation of A? peptide on the interface is a novel method for the treatment of AD.However,the aggregation mechanism and the dynamic process of the A?peptide molecule are still controversy.Thus this work focus on the aggregation mechanism of A? molecule on different interface.By regulating the fluidity,hydrophilic-hydrophobic property and the microstructural of the interface.This thesis mainly include the following two aspects.(1)A? aggregation on lipid membranes:Supporting lipid bilayer(SLB)with different mobility was prepared to simulate cytomembrane in vivo.The mobility distinction of lipids is root in phase inversion temperature(Tc),we called the lipids gel phase and fluid phase.We prepared a uniform and stable SLBs,and incubation A? peptide with SLBs in different time.Using AFM and TIRFM characterize the aggregation morphology and diffusion of A?peptide.The results indicate that gel phase membrane retards A? peptide fibrillation by restricting the 2D-mobility of peptide molecules on SLBs with less mobility,which lead A?peptide without enough time and space to reorganize.(2)A? aggregation on different interface:The hydrophobicity and the microstructure of the interface affect the aggregation of A? peptide.We regulated the hydrophobicity of interface by using PS-b-PHEMA as the interface material and realized the different hydrophobicity by controlling the block ratio.And regulated the microstructure of interface,coating the graphene oxide(GO)solution to a monofilm.All the above interface will incubation with A? peptide solution and observation by AFM.The results show that the polymer film induced A? peptide aggregation follows self-assembly method,and the assembly process is complex.? peptide aggregated on GO with slow rate,the aggregates morphology is spherical,but the detail mechanism need to be done.