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

Area of Science:

• Cell Biology
• Mechanobiology
• Molecular Biology

Background:

• Nuclear morphology varies during development and disease.
• The functional impact of nuclear shape on cell behavior remains largely unknown.

Purpose of the Study:

• To investigate the role of nuclear morphology in cell cycle progression.
• To elucidate the mechanisms by which nuclear shape influences cell behavior.

Main Methods:

• Observation of nuclear envelope flattening during the G1 to S phase transition.
• Inhibition of myosin II to study its effect on nuclear shape and cell cycle.
• Application of compressive force to the nucleus to assess its impact on cell cycle progression.
• Manipulation of nuclear morphology using various tools.
• Analysis of transcription factor activation (TEAD, AP1) and target gene induction.

Main Results:

• Nuclear envelope flattening occurs as cells transition from G1 to S phase.
• Myosin II inhibition prevents nuclear flattening and delays G1 to S progression.
• External compressive force can restore G1 to S transition even without myosin II.
• Nuclear flattening activates transcription factors TEAD and AP1, inducing genes that promote G1 to S transition.
• Nuclear flattening mediates TEAD and AP1 activation downstream of ROCK contractility and cell spreading.

Conclusions:

• The nuclear envelope functions as a mechanical sensor.
• Nuclear deformation regulates cell growth in response to mechanical tension.
• Nuclear shape is a critical regulator of cell cycle progression.