Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth
© 2020 National Academy of Sciences. All rights reserved. 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 p...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Proceedings of the National Academy of Sciences
2021
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| Online Access: | https://hdl.handle.net/1721.1/136160 |
| _version_ | 1826204460987187200 |
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| author | Mu, Luye Kang, Joon Ho Olcum, Selim Payer, Kristofor R Calistri, Nicholas L Kimmerling, Robert J Manalis, Scott R Miettinen, Teemu P |
| author_facet | Mu, Luye Kang, Joon Ho Olcum, Selim Payer, Kristofor R Calistri, Nicholas L Kimmerling, Robert J Manalis, Scott R Miettinen, Teemu P |
| author_sort | Mu, Luye |
| collection | MIT |
| description | © 2020 National Academy of Sciences. All rights reserved. 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. Sizedependent 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. |
| first_indexed | 2024-09-23T12:55:06Z |
| format | Article |
| id | mit-1721.1/136160 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:55:06Z |
| publishDate | 2021 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1361602021-10-28T03:58:50Z Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth Mu, Luye Kang, Joon Ho Olcum, Selim Payer, Kristofor R Calistri, Nicholas L Kimmerling, Robert J Manalis, Scott R Miettinen, Teemu P © 2020 National Academy of Sciences. All rights reserved. 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. Sizedependent 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. 2021-10-27T20:31:10Z 2021-10-27T20:31:10Z 2020 2021-09-07T17:58:26Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136160 en 10.1073/PNAS.1922197117 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Mu, Luye Kang, Joon Ho Olcum, Selim Payer, Kristofor R Calistri, Nicholas L Kimmerling, Robert J Manalis, Scott R Miettinen, Teemu P Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth |
| title | Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth |
| title_full | Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth |
| title_fullStr | Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth |
| title_full_unstemmed | Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth |
| title_short | Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth |
| title_sort | mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle and cell size dependent growth |
| url | https://hdl.handle.net/1721.1/136160 |
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