Gold Nanoparticles Control Conformation,Aggregation And Fibrillation Of Amylin

Type ? diabetes accounts for 90% of diabetes cases,which affecting more than 300 million people.Amylin plays a key role in the development of type ? diabetes.Aggregates formed by misfolding of amylin are toxic to islet ?-cells.In patients with type 2 diabetes,amyloid deposits were found in most of patients and are considered to be characteristic of type ? diabetes.In addition,amyloplast accumulation also leads to failure of human islet cell transplantation.Therefore,a non-toxic and effective drug that inhibits amylin fibration is important.At present,gold nanoparticles,with many unique physical and chemical properties such as high surface electron density,adjustable surface ligands,unique optical properties,and good biocompatibility,are also used in the study of protein fibration.Among the characteristics of gold nanoparticles,chirality is a special property,because biofilms in human are chiral,and this kind of chiral biofilm plays a certain role in the misfolding of amyloid in vivo.By synthesizing chiral gold nanoparticles,the authors simulated the effects of chiral biointerfaces on amyloid aggregation and fibration,which to explored the effects and mechanisms of chiral interfaces on amylin aggregation and better understand Neurodegenerative diseases and provide possible treatments.Chiral gold nanoparticle enantiomers with different chiralities and characterized were synthesized.They are measured by transmission electron microscopy,dynamic light scattering,ultraviolet-visible spectroscopy,infrared spectroscopy and X-ray photoelectron spectroscopy,which could comfirm that gold nanoparticles were synthesized successfully.The properties of the two chiral gold nanoparticles in these tests are almost identical.It was found by circular dichroism spectroscopy that the two chiral gold nanoparticles have a symmetric CD spectrum,which proves that the two gold nanoparticles are chiral enantiomers.The biocompatibility of gold nanoparticles was proved to be good by cytotoxicity experiments.The effects of gold nanoparticle concentration and chirality on amylin aggregation and fibrosis during incubation were measured by AFM,ThT fluorescence assay,DLS and CD spectrum by incubation of these two chiral gold nanoparticles with amylin in the same environment.It was found that gold nanoparticles can inhibit the fibrosis of amylin in a concentration-dependent method,and the efficiency and inhibition of amylin fibrosis by different chiral gold nanoparticles are also different.L-AuNPs can inhibit the conformational transition of amylin from random coil to ?-helical conformation,while D-AuNPs can inhibit the transformation of amylin from ?-helix to ?-sheet during the growth phase.These results reveal the role of chiral interface in controling amylin inhibition,helping us understand the reasons for the inhibition of amylin fibrosis by gold nanoparticles,and provide strategies for the study of anti-amyloidosis inhibitors for neurodegenerative diseases.