Theoretical and experimental evidence for hysteresis in cell proliferation.

Shaochun Bai, David Goodrich, C. Dennis Thron, Edwin Tecarro, Mandri Obeyesekere

Research output: Contribution to journalArticle


We propose a mathematical model for the regulation of the G1-phase of the mammalian cell cycle taking into account interactions of cyclin D/cdk4, cyclin E/cdk2, Rb and E2F. Mathematical analysis of this model predicts that a change in the proliferative status in response to a change in concentrations of serum growth factors will exhibit the property of hysteresis: the concentration of growth factors required to induce proliferation is higher than the concentration required to maintain proliferation. We experimentally confirmed this prediction in mouse embryonic fibroblasts in vitro. In agreement with the mathematical model, this indicates that changes in proliferative mode caused by small changes in concentrations of growth factors are not easily reversible. Based on this study, we discuss the importance of proliferation hysteresis for cell cycle regulation.

Original languageEnglish (US)
Pages (from-to)46-51
Number of pages6
JournalCell cycle (Georgetown, Tex.)
Issue number1
StatePublished - Jan 1 2003


ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Bai, S., Goodrich, D., Thron, C. D., Tecarro, E., & Obeyesekere, M. (2003). Theoretical and experimental evidence for hysteresis in cell proliferation. Cell cycle (Georgetown, Tex.), 2(1), 46-51.