Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth
Open Access
- 24 June 2020
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 117 (27), 15659-15665
- https://doi.org/10.1073/pnas.1922197117
Abstract
Cell size is believed to influence cell growth and metabolism. Consistently, several studies have revealed that large cells have lower mass accumulation rates per unit mass (i.e., growth efficiency) than intermediate-sized cells in the same population. Size-dependent growth is commonly attributed to transport limitations, such as increased diffusion timescales and decreased surface-to-volume ratio. However, separating cell size- and cell cycle-dependent growth is challenging. To address this, we monitored growth efficiency of pseudodiploid mouse lymphocytic leukemia cells during normal proliferation and polyploidization. This was enabled by the development of large-channel suspended microchannel resonators that allow us to monitor buoyant mass of single cells ranging from 40 pg (small pseudodiploid cell) to over 4,000 pg, with a resolution ranging from ∼1% to ∼0.05%. We find that cell growth efficiency increases, plateaus, and then decreases as cell cycle proceeds. This growth behavior repeats with every endomitotic cycle as cells grow into polyploidy. Overall, growth efficiency changes 33% throughout the cell cycle. In contrast, increasing cell mass by over 100-fold during polyploidization did not change growth efficiency, indicating exponential growth. Consistently, growth efficiency remained constant when cell cycle was arrested in G2. Thus, cell cycle is a primary determinant of growth efficiency. As growth remains exponential over large size scales, our work finds no evidence for transport limitations that would decrease growth efficiency.Keywords
Funding Information
- Samsung (-)
- HHS | NIH | National Cancer Institute (CA217377)
- Wellcome (110275/Z/15/Z)
This publication has 45 references indexed in Scilit:
- Direct observation of mammalian cell growth and size regulationNature Methods, 2012
- Physical limits of cells and proteomesProceedings of the National Academy of Sciences of the United States of America, 2011
- Recruitment of Cln3 Cyclin to Promoters Controls Cell Cycle Entry via Histone Deacetylase and Other TargetsPLoS Biology, 2009
- Cell Growth and Size Homeostasis in Proliferating Animal CellsScience, 2009
- The rate of cell growth is governed by cell cycle stageGenes & Development, 2009
- Limiting the Proliferation of Polyploid CellsCell, 2007
- Weighing of biomolecules, single cells and single nanoparticles in fluidNature, 2007
- Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1Proceedings of the National Academy of Sciences of the United States of America, 2006
- The origin of allometric scaling laws in biology from genomes to ecosystems: towards a quantitative unifying theory of biological structure and organizationJournal of Experimental Biology, 2005
- Ploidy evolution in the yeast Saccharomyces cerevisiae: a test of the nutrient limitation hypothesisJournal of Evolutionary Biology, 2001