Effect of Perfusion Culture on Localization, Intensity, and Functionality of Transporter Proteins in a Bilayer Proximal Tubule-on-a Chip

A biomimetic proximal tubule on-a-chip (PToC) comprised of isolated endothelial and epithelial microchannels along with a custom-made culture media perfusion system is presented. The microfluidic setup enables independently-addressable perfusion of epithelial and endothelial culture media for optimum bilayer health and function. It was shown for the first time that flow-induced shear stress not only enhances the expression level of megalin, a major proximal tubule transmembrane protein involved in albumin transcytosis, but also increases the chance of its presence/activity in the cytosol milieu. Albumin reabsorption capacity of the bilayer was improved through the epithelium subjected to shear stress, the cell height was increased, and the apical microvilli were fortified.