Nuclear envelope deformation controls cell cycle progression in response to mechanical force

EMBO Rep. 2019 Sep;20(9):e48084. doi: 10.15252/embr.201948084. Epub 2019 Aug 1.


The shape of the cell nucleus can vary considerably during developmental and pathological processes; however, the impact of nuclear morphology on cell behavior is not known. Here, we observed that the nuclear envelope flattens as cells transit from G1 to S phase and inhibition of myosin II prevents nuclear flattening and impedes progression to S phase. Strikingly, we show that applying compressive force on the nucleus in the absence of myosin II-mediated tension is sufficient to restore G1 to S transition. Using a combination of tools to manipulate nuclear morphology, we observed that nuclear flattening activates a subset of transcription factors, including TEAD and AP1, leading to transcriptional induction of target genes that promote G1 to S transition. In addition, we found that nuclear flattening mediates TEAD and AP1 activation in response to ROCK-generated contractility or cell spreading. Our results reveal that the nuclear envelope can operate as a mechanical sensor whose deformation controls cell growth in response to tension.

Keywords: TEAD; AP1; c-Jun; mechanotransduction; nuclear envelope.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Division / genetics
  • Cell Division / physiology
  • Cell Line
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Flow Cytometry
  • G1 Phase / genetics
  • G1 Phase / physiology
  • HeLa Cells
  • Humans
  • Mechanotransduction, Cellular / genetics
  • Mechanotransduction, Cellular / physiology*
  • Microscopy, Atomic Force
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism*
  • Plasmids / genetics
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • S Phase / genetics
  • S Phase / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • RNA, Small Interfering
  • Transcription Factors