Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro

Kévin Alessandri 1 Bibdu Ranjan Sinha 1 Vasily Valérïevitsch Gurchenkov 1, 2 Bidisha Sinha 3 Tobias Reinhold Kiessling 4 Luc Fetler 1 Felix Rico 5 Simon Scheuring 5 Christophe Lamaze 1, 2 Anthony Simon 1, 2 Sara Geraldo 1, 2 Danijela Vignjevicá 1, 2 Hugo Doméjean 6 Leslie Rolland 6 Anette Funfak 6 Jérôme Bibette 6 Nicolas Bremond 6 Pierre Nassoy 7, 1, *
* Auteur correspondant
1 PCC - Physico-Chimie-Curie
2 CDC - Compartimentation et dynamique cellulaires
3 IISER Kolkata - Indian Institute of Science Education and Research Kolbata
4 Soft Matter Physics Division [Leipzig, Allemagne]
5 Bio-AFM-Lab - BIO-AFM-LAB Bio Atomic Force Microscopy Laboratory
6 LCMD - Laboratoire Colloïdes et Matériaux Divisés
7 LP2N - Laboratoire Photonique, Numérique et Nanosciences
Abstract : Deciphering the multifactorial determinants of tumor progression requires standardized high-throughput preparation of 3D in vitro cellular assays. We present a simple microfluidic method based on the encapsulation and growth of cells inside permeable, elastic, hollow microspheres. We show that this approach enables mass production of size-controlled multicellular spheroids. Due to their geometry and elasticity, these microcapsules can uniquely serve as quantitative mechanical sensors to measure the pressure exerted by the expanding spheroid. By monitoring the growth of individual encapsulated spheroids after confluence, we dissect the dynamics of pressure buildup toward a steady-state value, consistent with the concept of homeostatic pressure. In turn, these confining conditions are observed to increase the cellular density and affect the cellular organization of the spheroid. Postconfluent spheroids exhibit a necrotic core cemented by a blend of extracellular material and surrounded by a rim of proliferating hypermotile cells. By performing invasion assays in a collagen matrix, we report that peripheral cells readily escape preconfined spheroids and cell–cell cohesivity is maintained for freely growing spheroids, suggesting that mechanical cues from the surrounding microenvironment may trigger cell invasion from a growing tumor. Overall, our technology offers a unique avenue to produce in vitro cell-based assays useful for developing new anticancer therapies and to investigate the interplay between mechanics and growth in tumor evolution. tissue mechanics | microfluidics | tumor growth | mechanotransduction
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Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2013, 110 (37), pp.14843-8. 〈10.1073/pnas.1309482110〉
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Kévin Alessandri, Bibdu Ranjan Sinha, Vasily Valérïevitsch Gurchenkov, Bidisha Sinha, Tobias Reinhold Kiessling, et al.. Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2013, 110 (37), pp.14843-8. 〈10.1073/pnas.1309482110〉. 〈inserm-01356886〉

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