Endothelial Cell Polarization and Orientation to Flow in a Novel Microfluidic Multimodal Shear Stress Generator

Abstract

<jats:p>Endothelial cells (EC) respond to shear stress to maintain vascular homeostasis, and a disrupted response is associated with cardiovascular diseases. To understand how different shear stress modalities affect EC morphology and behavior, we developed a microfluidic device that concurrently generates three different levels of uniform wall shear stress (WSS) and six different WSS gradients (WSSG). In this device, human umbilical vein endothelial cells (HUVECs) exhibited a rapid and robust response to WSS, with the relative positioning of the Golgi and nucleus transitioning from non-polarized to polarized in a WSS magnitude- and gradient-independent manner. By contrast, polarized HUVECs oriented their Golgi and nucleus polarity to the flow vector in a WSS magnitude-dependent manner, with positive WSSG inhibiting and negative WSSG promoting this upstream orientation. Having validated this device, this chip can now be used to dissect the mechanisms underlying EC responses to different WSS modalities, including shear stress gradients, and to investigate the influence of flow on a diverse range of cells during development, homeostasis and disease.</jats:p>

Remodeling of the Microvasculature: May the Blood Flow Be With You

“…Due to the geometrical versatility and high reproducibility and control that microfluidic devices offer, this technology springs as a promising tool for a better understanding of these events. For example, a recent microfluidic device was able to produce areas with three different constant shear stress values and six different shear stress gradients and showed that human endothelial cell upstream orientation depends on gradient direction (Sonmez et al, 2020). Following a top-down approach (Hesh et al, 2019), we propose two prototypes of hybrid devices that on one hand are inspired on real microvascular networks in which capillary pruning and splitting occurs (Figure 3A,B), mimicking their preferential H and Y geometries; and on the other, they incorporate predicted shear stress values and spatiotemporal gradients, as discussed along this review, whose tuning and dynamics could only be recapitulated in these systems ( Figure 3C).…”

Bioinformatic identification of hub genes and related transcription factors in low shear stress treated endothelial cells

“…(b): The results derived from HUVECs were consistent with the results in animal experiment. HUVECs cell line was used in different types of shear stress and signal pathways in previous papers [42,43]. However, I think the direct comparison of different cell types, including HUVECs and Arterial ECs, in shear stress research is very important in the future study.…”