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Vol. 28 No. 12 (2016): Vol 28 Issue 12

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Molecular Insights into Interactions of Human Islet Amyloid Polypeptide with Lipid Membranes using Atomic Force Microscopy and Fluorescence Microscopy

https://doi.org/10.14233/ajchem.2016.20124
M.B. Divakara
Centre for Incubation, Innovation Research and Consultancy, Jyothy Institute of Technology, Tataguni, Off Kanakapura Road, Bengaluru-560 082, India; Visvesvaraya Technological University-Research Resource Centre, Jnana Sangama, Belagavi-590 018, India
M.S. Santosh
Centre for Incubation, Innovation Research and Consultancy, Jyothy Institute of Technology, Tataguni, Off Kanakapura Road, Bengaluru-560 082, India
C.R. Ravi Kumar
Department of Basic Sciences, East West Institute of Technology, Bengaluru-560 091, India
B.L. Dhananjaya
Toxicology and Drug discovery Unit, Centre for Emerging Technologies, Jain Global Campus, Jakkasandra Post, Kanakapura Taluk, Ramanagara District-562 112, India
N. Reddy
Centre for Incubation, Innovation Research and Consultancy, Jyothy Institute of Technology, Tataguni, Off Kanakapura Road, Bengaluru-560 082, India

Corresponding Author(s) : M.S. Santosh

santoshgulwadi@gmail.com

Asian Journal of Chemistry, Vol. 28 No. 12 (2016): Vol 28 Issue 12

Abstract

Type 2 diabetes mellitus (T2DM) is a global disease, in which the human amylin protein aggregates to form human islet amylin polypeptide (hIAPP) non-fibrils that are cytotoxic to pancreatic b-cells. The transformational change in hIAPP is accompanied by amorphous amyloid deposits on planar lipid membranes where in ordered and disordered membranes differ in the process of oligomerization, which is consistent with pathological findings in diabetic subjects. Such a transformational change results in the formation of non-fibrils, which are cytotoxic. In this study, with the use of atomic force microscopy (AFM) and fluorescence microscope (FM), we investigate the surface interactions and sequential conversion of hIAPP from small oligomers to mature hIAPP non-fibrils. It is observed that prolonged incubation under 25 °C, prohibits the fibrillar extension and permits formation of non-fibrillar peptide aggregates. These atomic force microscopy and fluorescence microscope techniques help in differentiating the oligomer formation better in real time and indicates how oligomer finally leads to changes in membrane morphology. Hence, this combined (AFM and FM) approach offers new molecular insights into the etiology of diabetes that could be extended to investigate amylin aggregation, oligomerization and amyloid non-fibril formation in vivo at a subcellular resolution.

Keywords

Amyloid IAPP Type 2 diabetes Oligomer Peptide-membrane interactions
Divakara, M., Santosh, M., Kumar, C. R., Dhananjaya, B., & Reddy, N. (2016). Molecular Insights into Interactions of Human Islet Amyloid Polypeptide with Lipid Membranes using Atomic Force Microscopy and Fluorescence Microscopy. Asian Journal of Chemistry, 28(12), 2788–2792. https://doi.org/10.14233/ajchem.2016.20124
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