Directed biomechanical compressive forces enhance fusion efficiency in model placental trophoblast cultures

Parameshwar, Prabu Karthick; Li, Chen; Arnauts, Kaline; Jiang, Junqing; Rostami, Sabra; Campbell, Benjamin E; Lu, Hongyan; Rosenzweig, Derek Hadar; Vaillancourt, Cathy ORCID: https://orcid.org/0000-0003-0543-6244 et Moraes, Christopher (2024). Directed biomechanical compressive forces enhance fusion efficiency in model placental trophoblast cultures Scientific Reports , vol. 14 , nº 11312. pp. 1-12. DOI: 10.1038/s41598-024-61747-3.

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Résumé

The syncytiotrophoblast is a multinucleated structure that arises from fusion of mononucleated cytotrophoblasts, to sheath the placental villi and regulate transport across the maternal-fetal interface. Here, we ask whether the dynamic mechanical forces that must arise during villous development might influence fusion, and explore this question using in vitro choriocarcinoma trophoblast models. We demonstrate that mechanical stress patterns arise around sites of localized fusion in cell monolayers, in patterns that match computational predictions of villous morphogenesis. We then externally apply these mechanical stress patterns to cell monolayers and demonstrate that equibiaxial compressive stresses (but not uniaxial or equibiaxial tensile stresses) enhance expression of the syndecan-1 and loss of E-cadherin as markers of fusion. These findings suggest that the mechanical stresses that contribute towards sculpting the placental villi may also impact fusion in the developing tissue. We then extend this concept towards 3D cultures and demonstrate that fusion can be enhanced by applying low isometric compressive stresses to spheroid models, even in the absence of an inducing agent. These results indicate that mechanical stimulation is a potent activator of cellular fusion, suggesting novel avenues to improve experimental reproductive modelling, placental tissue engineering, and understanding disorders of pregnancy development.

Type de document:	Article
Mots-clés libres:	Placenta; Choriocarcinoma; Fusion; Mechanics; Compression
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	21 mai 2024 05:44
Dernière modification:	21 mai 2024 05:44
URI:	https://espace.inrs.ca/id/eprint/15673

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