Biophysical changes reduce energetic demand in growth factor–deprived lymphocytes
Name
Hecht-2016-Biophysical changes.pdf
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1.48 MB
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Checksum (MD5)
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Author(s)
Kim, Dong-Hwee
Wirtz, Denis
Hecht, Vivian Chaya
Sullivan, Lucas Bryan
Kimmerling, Robert John
Hosios, Aaron Marc
Stockslager, Max Andrew
Stevens, Mark M.
Kang, Joon Ho
Vander Heiden, Matthew G.
Date Issued
February 2016
Journal
The Journal of Cell Biology
Publisher
Rockefeller University Press, The
Citation
Hecht, Vivian C. et al. “Biophysical Changes Reduce Energetic Demand in Growth Factor–deprived Lymphocytes.” The Journal of Cell Biology 212.4 (2016): 439–447.
Version
Final published version
Abstract
Cytokine regulation of lymphocyte growth and proliferation is essential for matching nutrient consumption with cell state. Here, we examine how cellular biophysical changes that occur immediately after growth factor depletion promote adaptation to reduced nutrient uptake. After growth factor withdrawal, nutrient uptake decreases, leading to apoptosis.
Bcl-xL expression prevents cell death, with autophagy facilitating long-term cell survival. However, autophagy induction is slow relative to the reduction of nutrient uptake, suggesting that cells must engage additional adaptive mechanisms to respond initially to growth factor depletion. We describe an acute biophysical response to growth factor withdrawal, characterized by a simultaneous decrease in cell volume and increase in cell density, which occurs before autophagy initiation and is observed in both FL5.12 Bcl-xL cells depleted of IL-3 and primary CD8+ T cells depleted of IL-2 that are
differentiating toward memory cells. The response reduces cell surface area to minimize energy expenditure while conserving biomass, suggesting that the biophysical properties of cells can be regulated to promote survival under conditions of nutrient stress.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Department of Physics
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-ShareAlike 3.0
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DOI of Published Version
https://doi.org/10.1083/jcb.201506118
