title: Mechanical control of mitotic progression in single animal cells.
abstract: Despite the importance of mitotic cell rounding in tissue development and cell proliferation, there remains a paucity of approaches to investigate the mechanical robustness of cell rounding. Here we introduce ion beam-sculpted microcantilevers that enable precise force-feedback-controlled confinement of single cells while characterizing their progression through mitosis. We identify three force regimes according to the cell response: small forces (∼5 nN) that accelerate mitotic progression, intermediate forces where cells resist confinement (50-100 nN), and yield forces (>100 nN) where a significant decline in cell height impinges on microtubule spindle function, thereby inhibiting mitotic progression. Yield forces are coincident with a nonlinear drop in cell height potentiated by persistent blebbing and loss of cortical F-actin homogeneity. Our results suggest that a buildup of actomyosin-dependent cortical tension and intracellular pressure precedes mechanical failure, or herniation, of the cell cortex at the yield force. Thus, we reveal how the mechanical properties of mitotic cells and their response to external forces are linked to mitotic progression under conditions of mechanical confinement.
authors: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, 4058 Basel, Switzerland;
authors: Cedric J
authors: CJ
authors: Cattin
authors: Zentrum für Mikroskopie, University of Basel, 4056 Basel, Switzerland;
authors: Marcel
authors: M
authors: Düggelin
authors: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, 4058 Basel, Switzerland;
authors: David
authors: D
authors: Martinez-Martin
authors: Swiss Nanoscience Institute, University of Basel, 4056 Basel, Switzerland; Department of Physics, University of Basel, 4056 Basel, Switzerland;
authors: Christoph
authors: C
authors: Gerber
authors: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, 4058 Basel, Switzerland; daniel.mueller@bsse.ethz.ch martstew@mit.edu.
authors: Daniel J
authors: DJ
authors: Müller
authors: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, 4058 Basel, Switzerland; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 daniel.mueller@bsse.ethz.ch martstew@mit.edu.
authors: Martin P
authors: MP
authors: Stewart
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D048430:Cell Shape; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D059010:Single-Cell Analysis / Q000295:instrumentation* / Q000379:methods*; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D006657:Histones; D008164:Luminescent Proteins; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D000205:Actomyosin; D018995:Myosin Heavy Chains
keywords: cell confinement; cell cortex; mitotic arrest; mitotic cell rounding; mitotic progression