title: Quantification of the Influence of Endotoxins on the Mechanics of Adult and Neonatal Red Blood Cells.
abstract: In this study, we physically modeled the influence of endotoxin-induced sepsis symptoms on human red blood cells (RBCs) by quantifying the impact of endotoxins on the cell mechanics by the analysis of Fourier-transformed mean square amplitude of shape fluctuation, called flicker spectroscopy. With the aid of a microfluidic diffusion chamber, we noninvasively determined principal mechanical parameters of human RBCs in the absence and presence of endotoxins for individual RBCs for the first time. Because of the elongation of saccharide chain length of endotoxins, we found an increase in the morphological transition from discocytes to echinocytes, and monotonic changes in the mechanical parameters. Since septic shocks often cause lethal risks of neonates, we measured the mechanical parameters of neonatal RBCs, and compared them to those of adult RBCs. The quantitative comparison reveals that neonatal RBCs are more susceptible to the effect of endotoxins than adult RBCs. Furthermore, coincubation with the antiseptic peptide P19-2.5 (Aspidasept) with endotoxin results in a slight suppression of the impact of the endotoxin. The strategy proposed in our study can potentially be applied for the quantitative diagnosis of RBCs based on mechanical readouts.
authors.affiliation: †Department of Physics, Graduate School of Science, Kyoto University, 606-8502 Kyoto, Japan.|‡Institute of Physical Chemistry, University of Heidelberg, D69120 Heidelberg, Germany.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ito
authors.affiliation: §Department of Pediatrics, Clinic of Neonatology, University of Heidelberg, D69120 Heidelberg, Germany.
authors.forename: Navina
authors.initials: N
authors.lastname: Kuss
authors.affiliation: ∥Institute of Microstructure Technology (IMT), Karlsruhe Institute of Technology (KIT), 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Bastian E
authors.initials: BE
authors.lastname: Rapp
authors.affiliation: †Department of Physics, Graduate School of Science, Kyoto University, 606-8502 Kyoto, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ichikawa
authors.affiliation: ⊥Research Center Borstel, D23845 Borstel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gutsmann
authors.affiliation: ⊥Research Center Borstel, D23845 Borstel, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
authors.affiliation: §Department of Pediatrics, Clinic of Neonatology, University of Heidelberg, D69120 Heidelberg, Germany.
authors.forename: Johannes M B
authors.initials: JM
authors.lastname: Pöschl
authors.affiliation: ‡Institute of Physical Chemistry, University of Heidelberg, D69120 Heidelberg, Germany.|¶Institute for Integrated Cell-Material Science (WPI iCeMS), Kyoto University, 606-8501 Kyoto, Japan.
authors.forename: Motomu
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000375:Aging / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D001696:Biomechanical Phenomena; D004548:Elasticity / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D044085:Microfluidics; D008853:Microscopy; D013057:Spectrum Analysis
chemical_list: D000891:Anti-Infective Agents, Local; D004731:Endotoxins