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Area of Science:

  • Cell Biology
  • Biophysics
  • Molecular Mechanobiology

Background:

  • Nuclear lamins form a structural network within the nucleus.
  • The nuclear lamina is hypothesized to protect DNA from mechanical stress and transmit forces.
  • Direct measurement of mechanical forces on nuclear lamins at the protein level has been lacking.

Purpose of the Study:

  • To develop a novel technical approach for measuring mechanical forces on nuclear lamins.
  • To investigate the mechanical forces acting on the nuclear lamina and their regulation.

Main Methods:

  • Development of a nanobody-based intermolecular tension Förster Resonance Energy Transfer (FRET) biosensor.
  • Utilizing the biosensor to measure mechanical strain in lamin filaments.
  • Analyzing force dependencies on cellular parameters like nuclear volume and actomyosin contractility.

Main Results:

  • The nuclear lamina experiences significant mechanical forces.
  • These forces are modulated by nuclear volume, actomyosin contractility, LINC complex function, chromatin condensation, cell cycle stage, and epithelial-mesenchymal transition (EMT).
  • Substantial forces were also detected on nucleoplasmic lamins, suggesting their mechanical significance.

Conclusions:

  • A nanobody-based FRET biosensor enables direct measurement of mechanical forces on nuclear lamins.
  • Nuclear lamins play a crucial mechanical role within the nucleus, influenced by various cellular states.
  • This approach facilitates the study of mechanobiology in complex protein structures.