Biophysical changes reduce energetic demand in growth factor-deprived lymphocytes

Vivian C. Hecht, Lucas B. Sullivan, Robert J. Kimmerling, Dong Hwee Kim, Aaron M. Hosios, Max A. Stockslager, Mark M. Stevens, Joon Ho Kang, Denis Wirtz, Matthew G. Vander Heiden, Scott R. Manalis

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)439-447
Number of pages9
JournalJournal of Cell Biology
Volume212
Issue number4
DOIs
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Hecht, V. C., Sullivan, L. B., Kimmerling, R. J., Kim, D. H., Hosios, A. M., Stockslager, M. A., Stevens, M. M., Kang, J. H., Wirtz, D., Vander Heiden, M. G., & Manalis, S. R. (2016). Biophysical changes reduce energetic demand in growth factor-deprived lymphocytes. Journal of Cell Biology, 212(4), 439-447. https://doi.org/10.1083/jcb.201506118