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Adaptive reorientation of endothelial collectives in response to strain


Mature epithelial monolayers share the ability to coherently respond to external mechanical stimuli. Tissue remodeling requires cell shape changes and coordinated movements. Human endothelia provide an exquisite example of such emerging collective activities. As part of their function in maintaining body homeostasis under variable hemodynamic loadings, endothelial ensembles must dynamically adapt to wall shear stress and cyclic deformation. While cell alignment in response to various flow conditions and wall shear stress levels has been described in detail, less is known about collective endothelial remodeling under pure wall deformation. Here, using a custom-developed bioreactor, we exposed mature human endothelia to two distinct physiological levels of cyclic loading, generating overlapping gradients of strain. Endothelial cells remodeled and reoriented depending on the level of imposed strain yielding local variations of cell density. The tissue adaptation depended by the establishment of mature adherens junctions, which were reinforced by the polarized recruitment of the adaptor protein Vinculin. The pivotal role of cell-to-cell junctions was confirmed by the biochemical inhibition of vascular endothelial cadherin homotypic contacts, which impaired the collective remodeling. Together, our data establish wall deformation as an independent determinant of endothelial architecture with direct implications in vascular physiopathology.

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Publication details

The article was received on 18 May 2018, accepted on 03 Aug 2018 and first published on 06 Aug 2018

Article type: Paper
DOI: 10.1039/C8IB00092A
Citation: Integr. Biol., 2018, Accepted Manuscript
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    Adaptive reorientation of endothelial collectives in response to strain

    L. Bernardi, C. Giampietro, V. Marina, M. Genta, E. Mazza and A. Ferrari, Integr. Biol., 2018, Accepted Manuscript , DOI: 10.1039/C8IB00092A

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