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Issue 8, 2008
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Endothelial cell polarization and chemotaxis in a microfluidic device

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Abstract

The directed migration of endothelial cells is an early and critical step in angiogenesis, or new blood vessel formation. In this study, the polarization and chemotaxis of human umbilical vein endothelial cells (HUVEC) in response to quantified gradients of vascular endothelial growth factor (VEGF) were examined. To accomplish this, a microfluidic device was designed and fabricated to generate stable concentration gradients of biomolecules in a cell culture chamber while minimizing the fluid shear stress experienced by the cells. Finite element simulation of the device geometry produced excellent agreement with the observed VEGF concentration distribution, which was found to be stable across multiple hours. This device is expected to have wide applicability in the study of shear-sensitive cells such as HUVEC and non-adherent cell types as well as in the study of migration through three-dimensional matrices. HUVEC were observed to chemotax towards higher VEGF concentrations across the entire range of concentrations studied (18–32 ng mL−1) when the concentration gradient was 14 ng mL−1 mm−1. In contrast, shallow gradients (2 ng mL−1 mm−1) across the same concentration range were unable to induce HUVEC chemotaxis. Furthermore, while all HUVEC exposed to elevated VEGF levels (both in steep and shallow gradients) displayed an increased number of filopodia, only chemotaxing HUVEC displayed an asymmetric distribution of filopodia, with enhanced numbers of protrusions present along the leading edge. These results suggest a two-part requirement to induce VEGF chemotaxis: the VEGF absolute concentration enhances the total number of filopodia extended while the VEGF gradient steepness induces filopodia localization, cell polarization, and subsequent directed migration.

Graphical abstract: Endothelial cell polarization and chemotaxis in a microfluidic device

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Publication details

The article was received on 04 Jan 2008, accepted on 12 May 2008 and first published on 30 May 2008


Article type: Paper
DOI: 10.1039/B719788H
Citation: Lab Chip, 2008,8, 1292-1299
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    Endothelial cell polarization and chemotaxis in a microfluidic device

    A. Shamloo, N. Ma, M. Poo, L. L. Sohn and S. C. Heilshorn, Lab Chip, 2008, 8, 1292
    DOI: 10.1039/B719788H

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