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Micelle Formation by a Fragment of Human Islet Amyloid Polypeptide

Elizabeth Rhoades ^*  and Ari Gafni ^*  

^* Biophysics Research Division, Institute of Gerontology, and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109

Correspondence: Address reprint requests to Dr. Ari Gafni, Biophysics Research Div., University of Michigan, 930 N. University Ave., Ann Arbor, MI 48109-1055. Tel.: 734-936-2156; Fax: 34-936-2116; E-mail: arigafni{at}umich.edu.

Human islet amyloid polypeptide (hIAPP) is the major component of amyloid plaques found in the pancreatic islets of persons with type 2 diabetes mellitus. HIAPP belongs to the group of amyloidogenic proteins, characterized by their aggregation and deposition as fibrillar amyloid in various body tissues. The aggregation of amyloidogenic proteins is thought to occur via a common pathway, but currently no unifying kinetic model exists. In previous work, we presented a model of amyloid fibril formation formulated from our observations of the aggregation of an amyloidogenic fragment of hIAPP, amino acids 20–29. Our model is based on nucleation-dependent aggregation, modified by the formation of off-pathway hIAPP micelles. In the present study we confirm the presence of peptide micelles, and experimentally determine the critical micelle concentration in solutions of hIAPP fragments using three different techniques: conductivity, pH, and fluorescence. All three techniques yield a critical micelle concentration of 3–3.5 µM peptide. Furthermore, based on changes in the fluorescence intensity of a labeled peptide fragment as well as a decrease in solution pH as a result of deprotonation of the amino terminus, we conclude that the amino terminus of the fragment undergoes a significant change of environment upon micellization.

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