BioProject

The highly negatively charged endothelial surface glycocalyx (ESG) functions as mechano-sensor detecting shear forces generated by the blood flow on the luminal side of brain endothelial cells (ECs) and contributes to the physical barrier of the blood-brain barrier (BBB). More...

The highly negatively charged endothelial surface glycocalyx (ESG) functions as mechano-sensor detecting shear forces generated by the blood flow on the luminal side of brain endothelial cells (ECs) and contributes to the physical barrier of the blood-brain barrier (BBB). Despite the importance of ESG in the regulation of BBB permeability in physiological conditions and in diseases, this is an underresearched area. Microfluidic lab-on-a-chip (LOC) devices allow the study of BBB properties in dynamic conditions. We studied a BBB model, human endothelial cells derived from hematopoetic stem cells in co-culture with brain pericytes, in an LOC device to understand the role of fluid flow in the regulation of ESG-related genes and surface charge. The MACE gene sequencing study showed differentially expressed core protein genes of the ESG after fluid flow, as well as enriched pathways for the extracellular matrix molecules. We observed increased barrier properties, a higher intensity glycocalyx staining and a more negative surface charge of human brain ECs in dynamic conditions. Our study is the first to provide data on ESG of human ECs in an LOC device under dynamic conditions and confirm the importance of fluid flow for BBB culture models. Overall design: 8 samples were analysed by genome-wide gene expression profiling of endothelial cells cultured in microfluidic lab-on-a-chip devices under static or dynamic conditions (3 and 5 biological replicates, respectively) using the Rapid MACE-seq method to identify differentially expressed genes upon fluid flow. Less...