Functional Molecules Regulate Amyloid Peptide Assembled Structure And Mechanical Properties

Recently,aberrant amyloids aggregation is associated with many kinds of degenerative diseases,such as,Alzheimer's disease(AD),Parkinson disease(PD)and Type-II diabetes mellitus(T2D),Huntington's disease(HD).Among them,type II diabetes,also known as non insulin-dependent diabetes,and it is one of the most common way,accounts about for 90% of patients.A current challenge is the discovery of an efficient way to modulate amyloid aggregation and inhibit the toxicity of its aggregates.The human islet amyloid polypeptide(hIAPP)is a protein composed of 37 amino acids that aggregates to form amyloid deposits in the islets of Langerhans,which is related to Type-II diabetes mellitus(T2D),The decapeptide with sequence H2N-SNNFGAILSS-COOH(hIAPP20–29 fragment)is considered to be the core fibrillating region of hIAPP.So it is important to study how to regulate hIAPP20–29 fragment aggregation for looking for effective treatment.In this work,photoexcited porphyrins are successfully used to inhibit the fibrillation of hIAPP20–29 and degrade the hIAPP20–29 mature fibres.Insights on the inhibitory mechanism are explored by DCF and UV spectroscopy.These findings may establish a new avenue to inhibit the aggregation of amyloid peptide hIAPP and enrich the current selection of modulators.Specific contents are as follows:(1)The self-aggregation process of hIAPP20–29 was record by circular dichroism(CD),ThT fluorescence labeling and atomic force microscope(AFM)technology.(2)Islet amylioid polypeptide aggregation morphology was regulated by illumination,porphyrin,light-driven porphyrin and solution concentration changes.The nanomechanical properties of the co-assembly structure was recorded by PFQNM.The result indicate that porphyrin molecules can successfuly inhibit hIAPP20–29 aggregation under light illumination.As function of porphyrin concentration,the assembly structure of peptide-porphyrin tranfered from short silm fibres to thin film.At the same time,the Young's modulus would increase gradually with the increase of concentration of porphyrin,this result indicated that porphyrin got involved into coassembly structure.The photoexcited porphyrin inhibited the aggregation of amyloid peptide mainly due to the generation of reactive oxygen(ROS)by porphyrin that can disassociate the hydrogen bond between the peptide backbone.Retained inhibitory effect of photoexcited porphyrin on hIAPP20–29 aggregation without light irradiation.(3)Light-driven porphyrin was successfully used to degrade the mature fibres of hIAPP20–29,the result shown that photoexcited porphhyrin not only inbit hIAPP20–29 aggregation but also photodegrade hIAPP20–29.