Study On Regulation And Optical Properties Of Self-assembled Structure Of ?-Amyloid Peptide

Misfolding of proteins is associated with neurodegenerative diseases,and the self-assembly of amyloid ? peptides(AP)associated with Alzheimer's disease(AD)has been the target of much research.Although the main hypothesis of the etiology of AD currently focuses on A? oligomers,amyloid plaque is still a hallmark of AD.Nearly 30%-50%of people infected with human immunodeficiency virus(HIV)suffer from neurocognitive dysfunction due to the formation of amyloid plaques in the brain.This shows that HIV transactivator transcription(Tat)protein is related to the produce of AD.Therefore,it is of great significance to study the regulation of the self-assembly structure of A? peptide by Tat protein.On the other hand,some studies have shown that amyloid peptides can self-assembly into nanostructures by structure regulation,and their morphology structures include fibrils,films,nanotubes,hydrogels,and liquid crystals.These nanostructures have been used in nanowires,biosensors,and three-dimensional culture,environmental carbon capture,retroviral gene transfer,daylighting and catalysis.This thesis mainly discusses from the following aspects:In Chapter I:introduction.It introduces the relationship between AD with A?peptide and Tat protein,as well as the aggregation of amyloid and its influencing factors.It also summarizes the self-assembled nanostructures of amyloid peptides and their control methods.The properties and applications of amyloid peptide nanostructures are described in detail.Finally,it summarizes the purpose and significance of this thesis.In Chapter ?,we studied the regulation of Tat protein on A?3342 peptide self-assembled structure.Thioflavin T fluorescence(ThT),infrared(FTIR),circular dichroism(CD)and atomic force microscopy(AFM)techniques were used to study the effect of Tat on the assembly structure of A? peptide.The results show that with the increase of Tat concentration,the aggregation of A?3342 increases,and Tat protein can promote the formation of ?-sheet during the aggregation of A?33-42 peptide.In order to investigate whether Tat interacts directly with A?,the assembly structures of A? peptide co-incubated with Tat protein of different concentrations were observed using AFM high resolution imaging technology.The test results showed that they directly interacted to form a Tat-A? multifibrillar complex,and as the Tat concentration increased,the multifibrillar becomes larger and thicker.Tat protein can bind to the surface of A? fibrils,resulting in the development of A? fibrils from the original longitudinal extension to lateral aggregation,forming a Tat-A? multifibrillar structure with irregular height and width.In order to study the corresponding internal factors and biophysical properties(nanomechanical properties)that lead to this structural change,we used amplitude-frequency modulation viscoelastic imaging mode(AM-FM)mode of AFM to determine the Tat-A? nanomechanical properties of the fibril structure.The results show that there is a clear difference between the Tat-A? multifibrillar structure and A? fibril:when Tat protein is introduced,the Tat-A? multifibrillar structure is formed with a Young's modulus that is greater than.only A? fibril.The formed Tat-Ap multifibrillar has a higher Young's modulus value,which means that the increase in the thickness of the amyloid fibril is related to the increase in its hardness,and the increase in stiffness can be explained by the introduction of Tat protein,the ?-sheet in the fibril increase in structure.The presence of Tat promotes the growth of A? fibrils and the formation of ?-sheet,resulting in a significant increase in the lateral aggregation of fibrils and an improvement in mechanical properties.These studies will broaden our understanding of the pathogenesis of A? and provide opportunities to develop effective therapeutic strategies.In Chapter?,we study the regulation and optical properties of A?16-20 peptide self-assembly structure by chemical modification.Through the acetylation modification of A?16-20(denoted as Ac-A?16-20),the assembly structure was changed from nanofibril structure to a crystal structure of hundreds of microns in length,and self-assembly can be controlled by adjusting the pH value of the assembly environment reversible assembly of crystals.The crystal structure is self-assembled under neutral conditions.When the pH of the system is adjusted to acidic,the crystals are disassembled,and the solution is adjusted to neutral or weakly alkaline again,and the crystal structure can be reassembled and formed again.Characterization of the secondary structure of self-assembled crystals by CD and FTIR,as well as AFM high-resolution atomic lattice imaging,the results show that Ac-A? 16-20 crystals with?-sheet secondary structure are formed by single-layer microcrystalline layer assembly of.In addition,optical measurements show that Ac-A?16-20 assembled crystals have good optical waveguide and fluorescence characteristics,and that the first assembled and reassembled crystals have stable and strong green fluorescence.The development of this study has important guiding significance for chemical modification to regulate the self-assembly structure of peptides and the design of new optical waveguide devices.