Journal
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
Volume 18, Issue 1, Pages 94-100Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5cp05924k
Keywords
-
Funding
- ARC [CE140100036]
- NIH [R15ES022766-01A1]
- NSF [CBET-1232724]
- NHMRC [APP1071350]
- Australian Laureate Fellowship from the ARC
- Juvenile Diabetes Research Foundation (JDRF) fellowship
- Operational Infrastructure Support Scheme of the Government of Victoria
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1232724] Funding Source: National Science Foundation
Ask authors/readers for more resources
Human islet amyloid polypeptide (hIAPP or amylin) aggregation is directly associated with pancreatic p-cell death and subsequent insulin deficiency in type 2 diabetes (T2D). Since no cure is currently available for T2D, it is of great benefit to devise new anti aggregation molecules, which protect beta-cells against hIAPP aggregation-induced toxicity. Engineered nanoparticles have been recently exploited as anti-aggregation nanomedicines. In this work, we studied graphene oxide (GO) nanosheets for their potential for hIAPP aggregation inhibition by combining computational modeling, biophysical characterization and cell toxicity measurements. Using discrete molecular dynamics (DMD) simulations and in vitro studies, we showed that GO exhibited an inhibitory effect on hIAPP aggregation. DMD simulations indicated that the strong binding of hIAPP to GO nanosheets was driven by hydrogen bonding and aromatic stacking and that the strong peptide-GO binding efficiently inhibited hIAPP self-association and aggregation on the nanosheet surface. Secondary structural changes of hIAPP upon GO binding derived from DMD simulations were consistent with circular dichroism (CD) spectroscopy measurements. Transmission electron microscopy (TEM) images confirmed the reduction of hIAPP aggregation in the presence of GO. Furthermore, we carried out a cell toxicity assay and found that these nanosheets protected insulin-secreting NIT-1 pancreatic beta-cells against hIAPP-induced toxicity. Our multidisciplinary study suggests that GO nanosheets have the potential to be utilized as an anti-aggregation nanomedicine itself in addition to a biosensor or delivery vehicle for the mitigation of T2D progression.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available