Variable fluid flow regimes alter human brain microvascular endothelial c<scp>ell–cell</scp> junctions and cytoskeletal structure

Ranadewa, Dilshan; Wu, Jingwen; Subramanianbalachandar, Vignesh A.; Steward, Robert L.

doi:10.1002/cm.21687

Cited by 6 publications

(4 citation statements)

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“…Strikingly, the levels of plasma sJAM-A and EC-expressed JAM-A protein were reduced by the tumor inducers Tβ4 and TGF-β1, and the F11R/JAM-A antagonistic peptide 4D (P4D) showed a prospective barrier-protecting effect ( 145 ). The junction structure reorganization for JAM-A changed under low laminar flow conditions ( 146 ). Of note, JAM-A rearranged from interendothelial TJs to the luminal surface of blood vessels under acute blood flow variations, which implied JAM-A as a marker of acute endothelial activation and dysfunction ( 147 ).…”

Section: Junctional Adhesion Molecules and Atherosclerosismentioning

confidence: 99%

Junctional Adhesion Molecules: Potential Proteins in Atherosclerosis

Wang

Chen

2022

Front. Cardiovasc. Med.

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Junctional adhesion molecules (JAMs) are cell-cell adhesion molecules of the immunoglobulin superfamily and are involved in the regulation of diverse atherosclerosis-related processes such as endothelial barrier maintenance, leucocytes transendothelial migration, and angiogenesis. To combine and further broaden related results, this review concluded the recent progress in the roles of JAMs and predicted future studies of JAMs in the development of atherosclerosis.

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Section: Junctional Adhesion Molecules and Atherosclerosismentioning

confidence: 99%

Junctional Adhesion Molecules: Potential Proteins in Atherosclerosis

Wang

Chen

2022

Front. Cardiovasc. Med.

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“…Analysis of the localization and the phenotype of cell-cell junctions may offer additional insight into ECIS measurements under flow. Ranadewa et al showed that human cerebral microvascular endothelial cells exhibited a structural response to low fluid shear (1 dyn/cm 2 ) over 24 h 61 . They found that laminar flow induced the relocalization of cell-cell junctions such as ZO-1 and VE-cadherin toward the cell center, and that this level of shear also corresponded to significantly smaller cell size compared to static control.…”

Section: Discussionmentioning

confidence: 99%

A microfluidic platform with integrated porous membrane cell-substrate impedance spectroscopy (PM-ECIS) for biological barrier assessment

Ugodnikov,

Lu,

Chebotarev

et al. 2023

Preprint

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Traditionally, biological barriers are assessed in vitro by measuring trans-endothelial/epithelial electrical resistance (TEER) across a monolayer using handheld chopstick electrodes. Implementation of TEER into organ-on-chip (OOC) setups is a challenge however, due to non-uniform current distribution and interference from biomaterials typically found in such systems. In this work, we address the pitfalls of standard TEER measurement through the application of porous membrane electrical cell-substrate impedance sensing (PM-ECIS) to an OOC setup. Gold leaf electrodes (working electrode diameters = 250, 500, 750 µm) were incorporated onto porous membranes and combined with biocompatible tape to assemble microfluidic devices. PM-ECIS resistance at 4 kHz was not influenced by presence of collagen hydrogel in bottom channels, compared to TEER measurements in same devices, which showed a difference of 1723 ± 381.8 Ω (p=0.006) between control and hydrogel conditions. A proof of concept, multi-day co-culture model of the blood-brain barrier was also demonstrated in these devices. PM-ECIS measurements were robust to fluid shear (5 dyn/cm2) in cell-free devices, yet were highly sensitive to flow-induced changes in an endothelial barrier model. Initiation of perfusion (0.06 dyn/cm2) in HUVEC-seeded devices corresponded to significant decreases in impedance at 40 kHz (p<0.01 for 750 and 500 µm electrodes) and resistance at 4 kHz (p<0.05 for all electrode sizes) relative to static control cultures, with minimum values reached at 6.5 to 9.5 hours after induction of flow. Our microfluidic PM-ECIS platform enables sensitive, non-invasive, real-time measurements of barrier function in setups integrating critical OOC features like 3D co-culture, biomaterials and shear stress.

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“…As a result, the device provided a high-throughput ability for examining brain tumor metastases and its therapy responses. Hydrogels are commonly utilized as a substrate in self-assembled models because their low stiffness has been shown to enhance the formation of endothelial vascular networks ( Dessalles et al., 2021 ; Neuhaus, 2021 ; Ranadewa et al., 2021 ). For example, Li et al.…”

Section: In Vitro Models Of the Bbbmentioning

confidence: 99%