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Stiffness Increases Mononuclear Cell Transendothelial Migration

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Abstract

Cardiovascular diseases, including hypertension and the evolution of an atherosclerotic plaque alter the mechanics of the sub-endothelium. The extent to which either arterial softening or stiffening exacerbates or reduces mononuclear leukocyte infiltration from the bloodstream into the wall remains unclear. Mononuclear cell (MNC) transmigration was observed using an in vitro model of the inflamed human vascular endothelium on variable substrate stiffness. Briefly, human aortic endothelial cells were allowed to grow to confluency on gels of 1, 3, 5, 280 kPa, and on glass (~70 GPa), and then activated with TNF-α. Isolated human MNCs were allowed to transmigrate across the inflamed endothelium for 1 h. Fewer MNC transmigrated on soft compared to stiff substrates, yet the relative expression of ICAM-1 and VCAM-1, and the fraction of MNCs that become activated (or changed shape) did not change. Following MNC transendothelial migration the distribution of VCAM-1 is translocated from the apical to basal plasma membrane as revealed through immunofluorescence; since less MNCs transmigrate on soft subendothelial substrates, translocation of VCAM-1 was not observed. These results herein highlight that stiffer subendothelial substrates actually increase MNC transmigration, yet transmigration on stiff substrates can be abrogated by blocking ICAM-1.

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Abbreviations

MNC:

Mononuclear cell

HAEC:

Human aortic endothelial cell

TEM:

Transendothelial migration

MFI:

Mean fluorescent intensity

a.u.:

Arbitrary units

PMN:

Polymorphonuclear cell

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Acknowledgments

We gratefully apreciate UMD undergraduates Alex Paraloglou and Sruthi Rajarajan for performing immunofluoresence staining and analyzing data. We also thank Dr. Kim Stroka for technical assistance. Funding was provided by National Science Foundation CMMI-0643783 and Human Frontier Science Project Organization RGP0058/2012 (H.A.E.).

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The authors declare no competing financial interests.

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Authors and Affiliations

  1. Fischell Department of Bioengineering, University of Maryland, 3138 Jeong H. Kim Engineering Bldg., College Park, MD, 20742, USA

    Heather N. Hayenga & Helim Aranda-Espinoza

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  1. Heather N. Hayenga
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  2. Helim Aranda-Espinoza
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Correspondence to Helim Aranda-Espinoza.

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Associate Editor Mohammad R. K. Mofrad oversaw the review of this article.

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Hayenga, H.N., Aranda-Espinoza, H. Stiffness Increases Mononuclear Cell Transendothelial Migration. Cel. Mol. Bioeng. 6, 253–265 (2013). https://doi.org/10.1007/s12195-013-0284-9

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