Real-time estimation of paracellular permeability of cerebral endothelial cells by capacitance sensor array

Abstract

Vascular integrity is important in maintaining homeostasis of brain microenvironments. In various brain diseases including Alzheimer’s disease, stroke, and multiple sclerosis, increased paracellular permeability due to breakdown of blood-brain barrier is linked with initiation and progression of pathological conditions. We developed a capacitance sensor array to monitor dielectric responses of cerebral endothelial cell monolayer, which could be utilized to evaluate the integrity of brain microvasculature. Our system measured real-time capacitance values which demonstrated frequency- and time-dependent variations. With the measurement of capacitance at the frequency of 100 Hz, we could differentiate the effects of vascular endothelial growth factor (VEGF), a representative permeability-inducing factor, on endothelial cells and quantitatively analyse the normalized values. Interestingly, we showed differential capacitance values according to the status of endothelial cell monolayer, confluent or sparse, evidencing that the integrity of monolayer was associated with capacitance values. Another notable feature was that we could evaluate the expression of molecules in samples in our system with the reference of real-time capacitance values. We suggest that this dielectric spectroscopy system could be successfully implanted as a novel in vitro assay in the investigation of the roles of paracellular permeability in various brain diseases.

Real-time and label-free monitoring of nanoparticle cellular uptake using capacitance-based assays

“…4a ; dotted olive line). These results are consistent with our previous assertions that decreased capacitance is indicative of increased para-cellular permeability 25 .…”

Complex Tissue and Disease Modeling using hiPSCs

“…Blood flow simulation and peripheral immune cells can be also incorporated as challenges by integration in micron-scale hollow tubes lined with endothelial cells separated from the pericyte/ astrocyte or microglial components by thin porous membranes. Several prototypes of these ''BBB-on-a-chip'' devices have been described over the last 2 or 3 years (Booth and Kim, 2012;Brown et al, 2015;Cho et al, 2015;Deosarkar et al, 2015;Griep et al, 2013;Hyun Jo et al, 2015;Yeon et al, 2012). Future prototypes would incorporate not only the BBB compartment, but also a cerebral spinal fluid (CSF) compartment, currently being developed as part of the NIH-funded brain-on-chip program (Alcendor et al, 2013).…”

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