Membrane attack complex formation on a supported lipid bilayer: Initial steps towards a CARPA predictor nanodevice

Saziye Yorulmaz, Seyed R. Tabaei, Myunghee Kim, Jeongeun Seo, Walter Hunziker, J. Szebeni, Nam Joon Cho

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)245-255
Number of pages11
JournalEuropean Journal of Nanomedicine
Volume7
Issue number3
DOIs
Publication statusPublished - Jun 1 2015

Fingerprint

Complement Membrane Attack Complex
Lipid bilayers
Lipid Bilayers
attack
lipids
Chemical activation
activation
membranes
Membranes
predictions
Quartz Crystal Microbalance Techniques
Pharmaceutical Preparations
Nanomedicine
Complement Activation
drugs
Therapeutic Uses
Silicon
Protein C
Nanoparticles
proteins

Keywords

  • bedside diagnosis
  • complement
  • ELISA
  • hypersensitivity reactions
  • immune toxicity
  • solvent-Assisted lipid bilayer (SALB) formation method
  • support lipid bilayer

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Physical and Theoretical Chemistry
  • Biomedical Engineering

Cite this

Membrane attack complex formation on a supported lipid bilayer : Initial steps towards a CARPA predictor nanodevice. / Yorulmaz, Saziye; Tabaei, Seyed R.; Kim, Myunghee; Seo, Jeongeun; Hunziker, Walter; Szebeni, J.; Cho, Nam Joon.

In: European Journal of Nanomedicine, Vol. 7, No. 3, 01.06.2015, p. 245-255.

Research output: Contribution to journalArticle

Yorulmaz, Saziye ; Tabaei, Seyed R. ; Kim, Myunghee ; Seo, Jeongeun ; Hunziker, Walter ; Szebeni, J. ; Cho, Nam Joon. / Membrane attack complex formation on a supported lipid bilayer : Initial steps towards a CARPA predictor nanodevice. In: European Journal of Nanomedicine. 2015 ; Vol. 7, No. 3. pp. 245-255.
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