Colloquium: "Inhibiting Protein Amyloid Aggregation with Nanoparticles"Thursday, March 16, 2017 - 16:00 to 17:15
Dr. Feng Ding, Assistant Professor
Department of Physics and Astronomy
Clemson, South Carolina
Protein amyloid aggregation is associated with an increasing list of human diseases, including Amyotrophic Lateral Sclerosis, Alzheimer's Diseases, and Type-2 Diabetes (T2D). The hallmark of various amyloid diseases is the deposition of amyloid fibrils in human tissues formed by various disease-associated proteins. Despite differences in precursor protein sequences and structures, the final amyloid fibrils share the common cross-beta structure. Rapid advances in nanotechnology and nanomedicine open the opportunity of engineered nanoparticles that may be used to inhibit protein misfolding and aggregation. Combining computational modeling with experimental validation, we have established that PAMAM dendrimer and Graphene Oxide -- two classes of nanoparticles with many applications, such as drug loading, and biosensing -- have also anti-aggregation activities against the human islet amyloid polypeptide (hIAPP), the aggregation of which is implicated in T2D. Our computational studies predicted that both NPs have strong binding with hIAPP, which prevents their self-association and aggregation. In vitro and ex vivo also confirmed that the inhibition of hIAPP aggregation reduced the toxicity of hIAPP to pancreatic beta-cells.
To fully understand the complex effects of NPs on protein aggregation, we devised a simple course-grained model to study peptide aggregation in the presence of NPs. Our systematic computational study offers a molecular mechanism for delineating the contrasting and seemingly conflicting effects of NP-protein attraction on amyloid aggregation and highlights the potential of tailoring anti-aggregation nanomedicine against amyloid diseases.