| AVS 54th International Symposium | |
| Biomaterial Interfaces | Tuesday Sessions |
| Session BI-TuM |
| Session: | Proteins at Interfaces |
| Presenter: | M.B. Hovgaard, University of Aarhus, Denmark |
| Authors: | M.B. Hovgaard, University of Aarhus, Denmark M. Dong, University of Aarhus, Denmark D.E. Otzen, University of Aalborg, Denmark F. Besenbacher, University of Aarhus, Denmark |
| Correspondent: | Click to Email |
The ability of certain polypeptides to form amyloid aggregates and their subsequent deposition at plague sites has been associated with multiple protein folding disorders.1 As in vivo conditions associated with amyloid fibrillation are often dictated by surface and lipid membrane phenomena, the study of amyloid fibrillation at the solid-liquid interface represents an important and physiologically relevant approach to the study of amyloid fibrillogenesis. We have used Quartz Crystal Microbalance with Dissipation (QCM-D) to monitor the changes in layer surface mass density and viscoelastic properties accompanying multi-layer amyloid deposition in situ for the first time. By means of Atomic Force Microscope (AFM) imaging, an unequivocal correlation is established between the interfacial nucleation and growth of glucagon fibrils2 and the QCM-D response. The combination of the two techniques allows us to study the temporal evolution of the interfacial fibrillation process. We have modelled the QCM-D data using an extension to the Kelvin-Voigt viscoelastic model. Three phases were observed in the fibrillation process: I) A rigid multilayer of glucagon monomers forms and slowly rearranges; II) This multilayer subsequently evolves into a dramatically more viscoelastic layer, containing a polymorphic network of micrometer long fibrils growing from multiple nucleation sites; III) The fibrillar formation effectively stops, due to the depletion of bulk phase monomers, although the process can be continued without a lag phase by subsequent addition of fresh monomers. The robustness of the QCM-D technique, consolidated by complementary AFM studies, should make it possible to combine different components thought to be involved in the plaque formation process and thus build up realistic models of amyloid plaque formation in vitro.
1Frokjaer, S. and D.E. Otzen, Protein drug stability: A formulation challange, Nat Rev Drug Discov. 4, 298-306 (2005).
2M. Dong, M. B. Hovgaard, S. Xu, D. E Otzen, and F. Besenbacher, AFM Study of Glucagon Fibrillation Via Oligomeric Structures Resulting in Interwoven Fibrils. Nanotech. 17, 4003-4009 (2006).