Polarized Intestinal Cell Membrane‐on‐Chip for Bacterial Toxin Interaction Studies

The virulence of a pathogen is tied to the successful interaction between the pathogen, or its toxins, and the host cell. Polarized epithelial cells, constituting highly specialized cell monolayers, possess apical and basolateral membrane regions with distinct functions and structural compositions....

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Main Authors: Reece McCoy, Jeremy Treiber, George G. Malliaras, Alberto Salleo, Róisín M. Owens
Format: Article
Language:English
Published: Wiley-VCH 2025-03-01
Series:Advanced NanoBiomed Research
Subjects:
Online Access:https://doi.org/10.1002/anbr.202400135
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author Reece McCoy
Jeremy Treiber
George G. Malliaras
Alberto Salleo
Róisín M. Owens
author_facet Reece McCoy
Jeremy Treiber
George G. Malliaras
Alberto Salleo
Róisín M. Owens
author_sort Reece McCoy
collection DOAJ
description The virulence of a pathogen is tied to the successful interaction between the pathogen, or its toxins, and the host cell. Polarized epithelial cells, constituting highly specialized cell monolayers, possess apical and basolateral membrane regions with distinct functions and structural compositions. Preserving these intricacies in cell membrane‐on‐a‐chip platforms is important for retaining physiological relevance for investigating host–pathogen interactions. Consequently, a method for obtaining distinct populations of cell membrane vesicles representing the apical and basolateral membranes is presented here, in addition to the formation of their respective supported lipid bilayers (SLBs) on PEDOT:PSS conducting polymer electrodes. The apical localization of the A metalloprotease and disintegrin (ADAM10) receptor in Caco‐2 cells is shown to correlate with the increased response of the Staphylococcus aureus alpha hemolysin toxin on membrane‐on‐a‐chip platforms compared to the basolateral membrane model where the ADAM10 receptor is absent. The interaction between SLBs and the alpha hemolysin‐containing extracellular vesicles (EVs) secreted by S. aureus confirm the direct effect of toxin‐containing EVs on reducing the resistance of plasma membrane. This technique could find use in quantifying relative toxicity to the cell membrane, screening for cognate receptors and inhibitors, and probing toxin mechanism of action.
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spelling doaj-art-49ee7429b13646509e6450e960a3df302025-08-20T01:57:43ZengWiley-VCHAdvanced NanoBiomed Research2699-93072025-03-0153n/an/a10.1002/anbr.202400135Polarized Intestinal Cell Membrane‐on‐Chip for Bacterial Toxin Interaction StudiesReece McCoy0Jeremy Treiber1George G. Malliaras2Alberto Salleo3Róisín M. Owens4Department of Chemical Engineering and Biotechnology University of Cambridge Cambridge CB3 0AS UKDepartment of Materials Science and Engineering Stanford University Stanford CA 94305 USADepartment of Electrical Engineering University of Cambridge Cambridge CB3 0FA UKDepartment of Materials Science and Engineering Stanford University Stanford CA 94305 USADepartment of Chemical Engineering and Biotechnology University of Cambridge Cambridge CB3 0AS UKThe virulence of a pathogen is tied to the successful interaction between the pathogen, or its toxins, and the host cell. Polarized epithelial cells, constituting highly specialized cell monolayers, possess apical and basolateral membrane regions with distinct functions and structural compositions. Preserving these intricacies in cell membrane‐on‐a‐chip platforms is important for retaining physiological relevance for investigating host–pathogen interactions. Consequently, a method for obtaining distinct populations of cell membrane vesicles representing the apical and basolateral membranes is presented here, in addition to the formation of their respective supported lipid bilayers (SLBs) on PEDOT:PSS conducting polymer electrodes. The apical localization of the A metalloprotease and disintegrin (ADAM10) receptor in Caco‐2 cells is shown to correlate with the increased response of the Staphylococcus aureus alpha hemolysin toxin on membrane‐on‐a‐chip platforms compared to the basolateral membrane model where the ADAM10 receptor is absent. The interaction between SLBs and the alpha hemolysin‐containing extracellular vesicles (EVs) secreted by S. aureus confirm the direct effect of toxin‐containing EVs on reducing the resistance of plasma membrane. This technique could find use in quantifying relative toxicity to the cell membrane, screening for cognate receptors and inhibitors, and probing toxin mechanism of action.https://doi.org/10.1002/anbr.202400135organ‐on‐a‐chippathogensreceptorssupported lipid bilayerstoxins
spellingShingle Reece McCoy
Jeremy Treiber
George G. Malliaras
Alberto Salleo
Róisín M. Owens
Polarized Intestinal Cell Membrane‐on‐Chip for Bacterial Toxin Interaction Studies
Advanced NanoBiomed Research
organ‐on‐a‐chip
pathogens
receptors
supported lipid bilayers
toxins
title Polarized Intestinal Cell Membrane‐on‐Chip for Bacterial Toxin Interaction Studies
title_full Polarized Intestinal Cell Membrane‐on‐Chip for Bacterial Toxin Interaction Studies
title_fullStr Polarized Intestinal Cell Membrane‐on‐Chip for Bacterial Toxin Interaction Studies
title_full_unstemmed Polarized Intestinal Cell Membrane‐on‐Chip for Bacterial Toxin Interaction Studies
title_short Polarized Intestinal Cell Membrane‐on‐Chip for Bacterial Toxin Interaction Studies
title_sort polarized intestinal cell membrane on chip for bacterial toxin interaction studies
topic organ‐on‐a‐chip
pathogens
receptors
supported lipid bilayers
toxins
url https://doi.org/10.1002/anbr.202400135
work_keys_str_mv AT reecemccoy polarizedintestinalcellmembraneonchipforbacterialtoxininteractionstudies
AT jeremytreiber polarizedintestinalcellmembraneonchipforbacterialtoxininteractionstudies
AT georgegmalliaras polarizedintestinalcellmembraneonchipforbacterialtoxininteractionstudies
AT albertosalleo polarizedintestinalcellmembraneonchipforbacterialtoxininteractionstudies
AT roisinmowens polarizedintestinalcellmembraneonchipforbacterialtoxininteractionstudies