Endothelial cell polarization and orientation to flow in a novel microfluidic multimodal shear stress generator

Utku M. Sonmez; Ya-Wen Cheng; Simon C. Watkins; Beth L. Roman; Lance A. Davidson

doi:10.1039/D0LC00738B

Endothelial cell polarization and orientation to flow in a novel microfluidic multimodal shear stress generator†

Utku M. Sonmez,

^ad Ya-Wen Cheng,

^b Simon C. Watkins,^c Beth L. Roman

*^de and Lance A. Davidson

*^bfg

Author affiliations

* Corresponding authors

^a Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA

^b Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA
E-mail: lad43@pitt.edu

^c Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA

^d Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA
E-mail: romanb@edu

^e Vascular Medicine Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA

^f Department of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA

^g Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA

Abstract

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 a non-polarized to polarized state in a WSS magnitude- and gradient-dependent 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 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.

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DOI: https://doi.org/10.1039/D0LC00738B
Article type: Paper
Submitted: 21 Jul 2020
Accepted: 10 Oct 2020
First published: 20 Oct 2020

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Lab Chip, 2020,20, 4373-4390

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Endothelial cell polarization and orientation to flow in a novel microfluidic multimodal shear stress generator

U. M. Sonmez, Y. Cheng, S. C. Watkins, B. L. Roman and L. A. Davidson, Lab Chip, 2020, 20, 4373 DOI: 10.1039/D0LC00738B

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Endothelial cell polarization and orientation to flow in a novel microfluidic multimodal shear stress generator†

Abstract

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Endothelial cell polarization and orientation to flow in a novel microfluidic multimodal shear stress generator

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