Effect of DNA Origami Nanostructures on hIAPP Aggregation.

Marcel Hanke,Adrian Keller,Guido Grundmeier,Alejandro Gonzalez Orive

doi:10.3390/nano10112200

Marcel Hanke, Adrian Keller + Show 2 more

Open Access

https://doi.org/10.3390/nano10112200

Copy DOI

Journal: Nanomaterials	Publication Date: Nov 4, 2020
Citations: 9	License type: CC BY 4.0

Affiliation: Paderborn University, University of La Laguna

Abstract

The aggregation of human islet amyloid polypeptide (hIAPP) plays a major role in the pathogenesis of type 2 diabetes mellitus (T2DM), and numerous strategies for controlling hIAPP aggregation have been investigated so far. In particular, several organic and inorganic nanoparticles (NPs) have shown the potential to influence the aggregation of hIAPP and other amyloidogenic proteins and peptides. In addition to conventional NPs, DNA nanostructures are receiving more and more attention from the biomedical field. Therefore, in this work, we investigated the effects of two different DNA origami nanostructures on hIAPP aggregation. To this end, we employed in situ turbidity measurements and ex situ atomic force microscopy (AFM). The turbidity measurements revealed a retarding effect of the DNA nanostructures on hIAPP aggregation, while the AFM results showed the co-aggregation of hIAPP with the DNA origami nanostructures into hybrid peptide–DNA aggregates. We assume that this was caused by strong electrostatic interactions between the negatively charged DNA origami nanostructures and the positively charged peptide. Most intriguingly, the influence of the DNA origami nanostructures on hIAPP aggregation differed from that of genomic double-stranded DNA (dsDNA) and appeared to depend on DNA origami superstructure. DNA origami nanostructures may thus represent a novel route for modulating amyloid aggregation in vivo.

Highlights

The assembly of soluble protein andpeptide monomers into β-sheet-rich oligomeric and fibrillar amyloid aggregates is a fascinating and highly complex phenomenon [1], and of extraordinary relevance in biology and medicine
The turbidity measurements revealed a retarding effect of the DNA nanostructures on human islet amyloid polypeptide (hIAPP) aggregation, while the atomic force microscopy (AFM) results showed the co-aggregation of hIAPP with the DNA origami nanostructures into hybrid peptide–DNA aggregates
The effect of genomic double-stranded DNA (dsDNA) and two different DNA origami nanostructures on the aggregation of hIAPP was studied in situ and ex situ by turbidity measurements and AFM imaging, respectively

Summary

Introduction

The assembly of soluble protein and (poly)peptide monomers into β-sheet-rich oligomeric and fibrillar amyloid aggregates is a fascinating and highly complex phenomenon [1], and of extraordinary relevance in biology and medicine. The formation of oligomeric hIAPP as well as the growth of fibrils on the cell membranes of pancreatic β cells may lead to membrane damage and to β-cell death [7]. Despite their great molecular diversity, amyloid fibrils assembled from different molecules are surprisingly similar in morphology and molecular structure. Understanding and controlling the molecular mechanisms that govern amyloid aggregation in vivo have proven rather difficult [10,11]

Results

Discussion

Conclusion