Lipidation effect on surface adsorption and associated fibrillation of the model protein insulin

Sofie Fogh Hedegaard, Marite Cardenas (Lead / Corresponding author), Robert Barker, Lene Jorgensen, Marco van der Weert

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
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Lipidation of proteins is used in the pharmaceutical 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 homogenous network of fibrils covering the entire hydrophobic surface.
Original languageEnglish
Pages (from-to)7241-7249
Number of pages9
Issue number28
Early online date27 Jun 2016
Publication statusPublished - 19 Jul 2016


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