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

IF 4 Q2 ENGINEERING, BIOMEDICAL
Reece McCoy, Jeremy Treiber, George G. Malliaras, Alberto Salleo, Róisín M. Owens
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引用次数: 0

Abstract

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.

Abstract Image

极化肠细胞膜芯片用于细菌毒素相互作用研究
病原体的毒力取决于病原体或其毒素与宿主细胞之间的成功相互作用。极化上皮细胞构成高度特化的细胞单层,具有具有不同功能和结构组成的顶端和底侧膜区。在细胞膜芯片平台上保存这些复杂性对于保持研究宿主-病原体相互作用的生理相关性非常重要。因此,除了在PEDOT:PSS导电聚合物电极上形成各自的支持脂质双分子层(slb)外,本文还提出了一种获得代表顶膜和基底外侧膜的不同细胞膜囊泡群的方法。与缺乏ADAM10受体的基底外侧膜模型相比,Caco-2细胞中A金属蛋白酶和崩解素(ADAM10)受体的顶端定位与金黄色葡萄球菌α溶血素毒素在片上膜平台上的反应增加有关。slb与金黄色葡萄球菌分泌的含α溶血素的细胞外囊泡(EVs)的相互作用证实了含毒素的EVs对降低质膜耐药性的直接作用。该技术可用于定量测定对细胞膜的相对毒性,筛选同源受体和抑制剂,探索毒素的作用机制。
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来源期刊
Advanced Nanobiomed Research
Advanced Nanobiomed Research nanomedicine, bioengineering and biomaterials-
CiteScore
5.00
自引率
5.90%
发文量
87
审稿时长
21 weeks
期刊介绍: Advanced NanoBiomed Research will provide an Open Access home for cutting-edge nanomedicine, bioengineering and biomaterials research aimed at improving human health. The journal will capture a broad spectrum of research from increasingly multi- and interdisciplinary fields of the traditional areas of biomedicine, bioengineering and health-related materials science as well as precision and personalized medicine, drug delivery, and artificial intelligence-driven health science. The scope of Advanced NanoBiomed Research will cover the following key subject areas: ▪ Nanomedicine and nanotechnology, with applications in drug and gene delivery, diagnostics, theranostics, photothermal and photodynamic therapy and multimodal imaging. ▪ Biomaterials, including hydrogels, 2D materials, biopolymers, composites, biodegradable materials, biohybrids and biomimetics (such as artificial cells, exosomes and extracellular vesicles), as well as all organic and inorganic materials for biomedical applications. ▪ Biointerfaces, such as anti-microbial surfaces and coatings, as well as interfaces for cellular engineering, immunoengineering and 3D cell culture. ▪ Biofabrication including (bio)inks and technologies, towards generation of functional tissues and organs. ▪ Tissue engineering and regenerative medicine, including scaffolds and scaffold-free approaches, for bone, ligament, muscle, skin, neural, cardiac tissue engineering and tissue vascularization. ▪ Devices for healthcare applications, disease modelling and treatment, such as diagnostics, lab-on-a-chip, organs-on-a-chip, bioMEMS, bioelectronics, wearables, actuators, soft robotics, and intelligent drug delivery systems. with a strong focus on applications of these fields, from bench-to-bedside, for treatment of all diseases and disorders, such as infectious, autoimmune, cardiovascular and metabolic diseases, neurological disorders and cancer; including pharmacology and toxicology studies.
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