Vasily Gurchenkov, Felix Rico, Jérôme Bibette, Hugo Doméjean, Tobias Kießling, Bibhu Ranjan Sarangi, Leslie Rolland, Simon Scheuring, Luc Fetler, Sara Geraldo, Danijela Matic Vignjevic, Bidisha Sinha, Pierre Nassoy, Anthony Simon, Kevin Alessandri, Nicolas Bremond, Anette Funfak, Christophe Lamaze, Physico-Chimie-Curie (PCC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Compartimentation et dynamique cellulaires (CDC), Soft Matter Physics Division, University of Leipzig, Universität Leipzig [Leipzig], BIO-AFM-LAB Bio Atomic Force Microscopy Laboratory (Bio-AFM-Lab), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Colloïdes et Matériaux Divisés (LCMD), Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), lp2n-04,lp2n-16, Laboratoire Photonique, Numérique et Nanosciences (LP2N), Université Sciences et Technologies - Bordeaux 1-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Indian Institute of Science Education and Research Kolbata (IISER Kolkata), Soft Matter Physics Division [Leipzig, Allemagne], Universität Leipzig, Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS), LP2N_G3, LP2N_A3, Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), and Aix-Marseille Université, U1006
International audience; 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