Lipidation Effect on Surface Adsorption and Associated Fibrillation of the Model Protein Insulin

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Lipidation Effect on Surface Adsorption and Associated Fibrillation of the Model Protein Insulin

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Publication Article, peer reviewed scientific
Title Lipidation Effect on Surface Adsorption and Associated Fibrillation of the Model Protein Insulin
Author(s) Hedegaard, Sofie ; Cardenas, Marite ; Barker, Robert ; Jorgensen, Lene ; Van de Weert, Marco
Date 2016
English abstract
Lipidation of proteins is used in the pharma- ceutical field to increase the therapeutic efficacy of proteins. In this study, we investigate the effect of a 14-carbon fatty acid modification on the adsorption behavior of human insulin to a hydrophobic solid surface and the subsequent fibrillation development under highly acidic conditions and elevated temperature by comparing to the fibrillation of human insulin. At these stressed conditions, the lipid modification accelerates the rate of fibrillation in bulk solution. With the use of several complementary surface-sensitive techniques, including quartz crystal microbalance with dissipation monitoring (QCM-D), atomic force microscopy (AFM), and neutron reflectivity (NR), we show that there are two levels of structurally different protein organization at a hydrophobic surface for both human insulin and the lipidated analogue: a dense protein layer formed within minutes on the surface and a diffuse outer layer of fibrillar structures which took hours to form. The two layers may only be weakly connected, and proteins from both layers are able to desorb from the surface. The lipid modification increases the protein surface coverage and the thickness of both layer organizations. Upon lipidation not only the fibrillation extent but also the morphology of the fibrillar structures changes from fibril clusters on the surface to a more homogeneous network of fibrils covering the entire hydrophobic surface.
DOI http://dx.doi.org/10.1021/acs.langmuir.6b00522 (link to publisher's fulltext.)
Publisher ACS
Host/Issue Langmuir;28
Volume 32
ISSN 0743-7463
Pages 7241−7249
Language eng (iso)
Subject(s) Sciences
Research Subject Categories::NATURAL SCIENCES
Handle http://hdl.handle.net/2043/21271 (link to this page)

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