title: Physical confinement signals regulate the organization of stem cells in three dimensions.
abstract: During embryogenesis, the spherical inner cell mass (ICM) proliferates in the confined environment of a blastocyst. Embryonic stem cells (ESCs) are derived from the ICM, and mimicking embryogenesis in vitro, mouse ESCs (mESCs) are often cultured in hanging droplets. This promotes the formation of a spheroid as the cells sediment and aggregate owing to increased physical confinement and cell-cell interactions. In contrast, mESCs form two-dimensional monolayers on flat substrates and it remains unclear if the difference in organization is owing to a lack of physical confinement or increased cell-substrate versus cell-cell interactions. Employing microfabricated substrates, we demonstrate that a single geometric degree of physical confinement on a surface can also initiate spherogenesis. Experiment and computation reveal that a balance between cell-cell and cell-substrate interactions finely controls the morphology and organization of mESC aggregates. Physical confinement is thus an important regulatory cue in the three-dimensional organization and morphogenesis of developing cells.
authors: Department of Biology, University of Ottawa, Gendron Hall, 30 Marie Curie, Ottawa, Ontario, Canada K1N 6N5.
authors: Sebastian V
authors: 0000-0003-2901-197X
authors: SV
authors: Hadjiantoniou
authors: Department of Physics, University of Ottawa, MacDonald Hall, 150 Louis Pasteur, Ottawa, Ontario, Canada K1N 6N5.
authors: David
authors: D
authors: Sean
authors: Department of Physics, University of Ottawa, MacDonald Hall, 150 Louis Pasteur, Ottawa, Ontario, Canada K1N 6N5.
authors: Maxime
authors: M
authors: Ignacio
authors: Department of Physics, University of Ottawa, MacDonald Hall, 150 Louis Pasteur, Ottawa, Ontario, Canada K1N 6N5.|Department of Mechanical Engineering, University of Ottawa, Site Building, 800 King Edward Avenue, Ottawa, Ontario, Canada K1N 6N5.|Ottawa-Carleton Institute for Biomedical Engineering, Ottawa, Ontario, Canada K1N 6N5.
authors: Michel
authors: M
authors: Godin
authors: Department of Physics, University of Ottawa, MacDonald Hall, 150 Louis Pasteur, Ottawa, Ontario, Canada K1N 6N5.
authors: Gary W
authors: GW
authors: Slater
authors: Department of Biology, University of Ottawa, Gendron Hall, 30 Marie Curie, Ottawa, Ontario, Canada K1N 6N5 a@pellinglab.net.|Department of Physics, University of Ottawa, MacDonald Hall, 150 Louis Pasteur, Ottawa, Ontario, Canada K1N 6N5.|Institute for Science, University of Ottawa, Society and Policy, Desmarais Building, 55 Laurier Avenue East, Ottawa, Ontario, Canada K1N 6N5.
authors: Andrew E
authors: AE
authors: Pelling
mesh_terms: D000818:Animals; D002449:Cell Aggregation; D002460:Cell Line; D003198:Computer Simulation; D051379:Mice; D008954:Models, Biological; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism*
keywords: biophysics; biotechnology; cell biology; molecular biology; stem cells