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Dynamics of Endothelial Engagement and Filopodia Formation in Complex 3D Microscaffolds

Article dans une revue avec comité de lecture
Author
UCLA, Pierre
300372 Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL [ENSCP]
JU, Xingming
300372 Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL [ENSCP]
DEMIRCIOGLU, Melisa
300372 Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL [ENSCP]
BAIZ, Sarah
86289 Laboratoire Procédés et Ingénierie en Mécanique et Matériaux [PIMM]
MULLER, Laurent
139750 Centre interdisciplinaire de recherche en biologie [CIRB]
GERMAIN, Stéphane
139750 Centre interdisciplinaire de recherche en biologie [CIRB]
MONNOT, Catherine
139750 Centre interdisciplinaire de recherche en biologie [CIRB]
SEMETEY, Vincent
300372 Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL [ENSCP]
COSCOY, Sylvie
541732 Laboratoire Physico-Chimie Curie [Institut Curie] [PCC]

URI
http://hdl.handle.net/10985/22203
DOI
10.3390/ijms23052415
Date
2022-02-22
Journal
International Journal of Molecular Sciences

Abstract

The understanding of endothelium–extracellular matrix interactions during the initiation of new blood vessels is of great medical importance; however, the mechanobiological principles governing endothelial protrusive behaviours in 3D microtopographies remain imperfectly understood. In blood capillaries submitted to angiogenic factors (such as vascular endothelial growth factor, VEGF), endothelial cells can transiently transdifferentiate in filopodia-rich cells, named tip cells, from which angiogenesis processes are locally initiated. This protrusive state based on filopodia dynamics contrasts with the lamellipodia-based endothelial cell migration on 2D substrates. Using two-photon polymerization, we generated 3D microstructures triggering endothelial phenotypes evocative of tip cell behaviour. Hexagonal lattices on pillars (“open”), but not “closed” hexagonal lattices, induced engagement from the endothelial monolayer with the generation of numerous filopodia. The development of image analysis tools for filopodia tracking allowed to probe the influence of the microtopography (pore size, regular vs. elongated structures, role of the pillars) on orientations, engagement and filopodia dynamics, and to identify MLCK (myosin light-chain kinase) as a key player for filopodia-based protrusive mode. Importantly, these events occurred independently of VEGF treatment, suggesting that the observed phenotype was induced through microtopography. These microstructures are proposed as a model research tool for understanding endothelial cell behaviour in 3D fibrillary networks.

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