Abstract
In higher eukaryotes, epithelial cell layers line most body cavities and form selective barriers that regulate the exchange of solutes between compartments. In order to fulfil these functions, the cells assume a polarised architecture and maintain two distinct plasma membrane domains, the apical domain facing the lumen and the basolateral domain facing other cells and the extracellular matrix. Microfluidic biochips offer the unique opportunity to establish novel in vitro models of epithelia in which the in vivo microenvironment of epithelial cells is precisely reconstituted. In addition, analytical tools to monitor biologically relevant parameters can be directly integrated on-chip. In this review we summarise recently developed biochip designs for culturing epithelial cell layers. Since endothelial cell layers, which line blood vessels, have similar barrier functions and polar organisation as epithelial cell layers, we also discuss biochips for culturing endothelial cell layers. Furthermore, we review approaches to integrate tools to analyse and manipulate epithelia and endothelia in microfluidic biochips; including methods to perform electrical impedance spectroscopy; methods to detect substances undergoing trans-epithelial transport via fluorescence, spectrophotometry, and mass spectrometry; techniques to mechanically stimulate cells via stretching and fluid flow-induced shear stress; and methods to carry out high-resolution imaging of vesicular trafficking using light microscopy. Taken together, this versatile microfluidic toolbox enables novel experimental approaches to characterise epithelial monolayers.
Highlights
Epithelial cells constitute the key functional component of most body organs and organise themselves as selective barriers between the internal medium of the organism and various organ luminal compartments.[1]
In order to generate well-differentiated epithelial cell layers in vitro, it is necessary to reconstitute their natural microenvironment as closely as possible. This is traditionally achieved by culturing epithelial cells on Transwell lters,[1] which allow provision of different culture media to each side of a twodimensional epithelial cell layer. Another commonly utilised approach is based on placing epithelial cells, such as Madin– Darby canine kidney (MDCK) cells[16,17] or Michigan Cancer Foundation-7 (MCF-7) cells,[18] in gels resembling the extracellular matrix, where they form self-organised three-dimensional cysts with internal lumina
We highlight micro uidic models of lung epithelium, because there are impressive examples available that illustrate the potential of highly integrated micro uidic biochips to resemble complex epithelial cell layer functions on-chip
Summary
Epithelial cells constitute the key functional component of most body organs and organise themselves as selective barriers between the internal medium of the organism and various organ luminal compartments (gut lumen, urinary space, lung air space, lumina of exocrine and endocrine glands, etc.).[1]. This is traditionally achieved by culturing epithelial cells on Transwell lters,[1] which allow provision of different culture media to each side of a twodimensional epithelial cell layer Another commonly utilised approach is based on placing epithelial cells, such as Madin– Darby canine kidney (MDCK) cells[16,17] or Michigan Cancer Foundation-7 (MCF-7) cells,[18] in gels resembling the extracellular matrix, where they form self-organised three-dimensional cysts with internal lumina. His research focuses on host–pathogen interactions; in particular, he is interested in understanding the physiological role of bacterial lectins in mammalian cells by using analytical and synthetic approaches He studied chemistry and biology at the University of Regensburg, Germany. This review aims to provide an overview for both, biologists interested in novel techniques, and chemists, physicists and engineers interested in nding biologically relevant applications for their innovations, in order to stimulate inter-disciplinary exchange
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