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Title: Membrane attack complex formation on a supported lipid bilayer: initial steps towards a CARPA predictor nanodevice
Authors: Yorulmaz, Saziye
Tabaei, Seyed R.
Kim, Myunghee
Seo, Jeongeun
Hunziker, Walter
Szebeni, János
Cho, Nam-Joon
Keywords: Complement
Solvent-assisted lipid bilayer (SALB) formation method
Support lipid bilayer
Bedside diagnosis
Hypersensitivity reactions
Immune toxicity
Issue Date: 2015
Source: Yorulmaz, S., Tabaei, S. R., Kim, M., Seo, J., Hunziker, W., Szebeni, J., et al. (2015). Membrane attack complex formation on a supported lipid bilayer: initial steps towards a CARPA predictor nanodevice. European Journal of Nanomedicine, 7(3), 245-255.
Series/Report no.: European Journal of Nanomedicine
Abstract: The rapid advance of nanomedicines and biologicals in pharmacotherapy gives increasing importance to a common adverse effect of these modern therapeutics: complement (C) activation-related pseudoallergy (CARPA). CARPA is a relatively frequent and potentially lethal acute immune toxicity of many intravenous drugs that contain nanoparticles or proteins, whose prediction by laboratory or in vivo testing has not yet been solved. Preliminary studies suggest that proneness of the drug to cause C activation in the blood of patients may predict the individual risk of CARPA, thus, a sensitive and rapid bedside assay for individualized assessment of a drug’s C activating potential could alleviate the CARPA problem. The goal of the present study was to lay down the foundations of a novel approach for real-time sensing of C activation on a supported lipid bilayer platform. We utilized the quartz crystal microbalance with dissipation (QCM-D) monitoring technique to measure the self-assembly of C terminal complex (or membrane attack complex [MAC]) on supported lipid bilayers rapidly assembled by the solvent-assisted lipid bilayer (SALB) formation method, as an immediate measure of C activation. By measuring the changes in frequency and energy dissipation of deposited protein, the technique allows extremely sensitive real-time quantification of the sequential assembly of MAC from its molecular components (C5b-6, C7, C8 and C9) and hence, measure C activation in the ambient medium. The present paper delineates the technique and our initial evidence with purified C proteins that the approach enables sensitive and rapid (real-time) quantification of MAC formation on a silicon-supported planar (phospho) lipid bilayer, which can be used as an endpoint in a clinically useful bedside C activation assay.
ISSN: 1662-5986
DOI: 10.1515/ejnm-2015-0016
Schools: School of Materials Science & Engineering 
Rights: © 2015 European Journal of Nanomedicine (EJNM). This paper was published in European Journal of Nanomedicine and is made available as an electronic reprint (preprint) with permission of European Journal of Nanomedicine (EJNM). The published version is available at: []. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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