Mammalian cell growth dynamics in mitosis
Abstract
The extent and dynamics of animal cell biomass accumulation during mitosis are unknown, primarily because growth has not been quantified with sufficient precision and temporal resolution. Using the suspended microchannel resonator and protein synthesis assays, we quantify mass accumulation and translation rates between mitotic stages on a single-cell level. For various animal cell types, growth rates in prophase are commensurate with or higher than interphase growth rates. Growth is only stopped as cells approach metaphase-to-anaphase transition and growth resumes in late cytokinesis. Mitotic arrests stop growth independently of arresting mechanism. For mouse lymphoblast cells, growth in prophase is promoted by CDK1 through increased phosphorylation of 4E-BP1 and cap-dependent protein synthesis. Inhibition of CDK1-driven mitotic translation reduces daughter cell growth. Overall, our measurements counter the traditional dogma that growth during mitosis is negligible and provide insight into antimitotic cancer chemotherapies.
Data availability
All L1210 control buoyant mass measurement around M-phase, which were used for quantification of mitotic growth (Figure 1), MAR/mass dynamics (Figure 2), can be found in Figure 1-source data 1.
Article and author information
Author details
Funding
Wellcome (110275/Z/15/Z)
- Teemu P Miettinen
National Cancer Institute (CA217377)
- Scott R Manalis
Koch Institute Frontier Research Program (P30-CA14051)
- Scott R Manalis
Samsung
- Joon Ho Kang
The authors declare that the funders had no involvement in study design, data collection, interpretation or presentation.
Reviewing Editor
- Jon Pines, Institute of Cancer Research Research, United Kingdom
Version history
- Received: December 24, 2018
- Accepted: May 5, 2019
- Accepted Manuscript published: May 7, 2019 (version 1)
- Version of Record published: May 24, 2019 (version 2)
Copyright
© 2019, Miettinen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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