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Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans
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Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans

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Proteostatic defect drives biophysical remodeling that triggers cell competition

Wonjae Song1, Mai Yukitake1, Kei Kozawa1

  • 1Department of Molecular Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.

Iscience
|July 28, 2026
PubMed

Insights

Ribosomal protein insufficiency triggers cell competition by disrupting protein homeostasis and altering cell biophysics. Chemical chaperones can reverse these "loser" traits, preventing cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Cell competition is a vital tissue-surveillance mechanism where unfit cells are eliminated by fitter neighbors.
  • Understanding the molecular and biophysical underpinnings of this process is crucial for tissue homeostasis.

Purpose of the Study:

  • To establish a mammalian epithelial model for studying cell competition induced by ribosomal protein insufficiency.
  • To investigate the role of proteostasis disruption and biophysical changes in competitive cell elimination.

Main Methods:

  • Utilized Madin-Darby canine kidney (MDCK) cells with tetracycline-inducible shRNA targeting ribosomal protein large subunit 24 (Rpl24).
  • Co-cultured Rpl24-knockdown cells with normal cells to induce cell competition.
  • Administered 4-phenylbutyric acid (4-PBA) to assess its effect on proteostasis and cell competition.
  • Analyzed cellular biophysical properties including density, area, and cell-surface tension.

Main Results:

  • Rpl24 knockdown induced apoptosis in MDCK cells via cell competition with normal neighbors.
  • Ribosomal protein insufficiency disrupted protein homeostasis, leading to cytoplasmic protein aggregates.
  • 4-phenylbutyric acid (4-PBA) reduced aggregate accumulation and competitive cell death.
  • Proteostasis disruption caused significant biophysical changes in loser cells, including lower homeostatic density, increased cell area, and reduced cell-surface tension.
  • 4-PBA treatment reversed these observed biophysical alterations.

Conclusions:

  • Ribosomal protein insufficiency links proteostatic stress to distinct biophysical "loser" traits.
  • Proteostasis-dependent biophysical remodeling is a key factor in the elimination of cells during competition.
  • Targeting proteostasis and associated biophysical changes offers a potential strategy to modulate cell competition.
Keywords:
Ribosomal Protein Rpl24apoptosiscell competitioncellular biophysical alterationsmammalian cell culturep53proteostasis

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