Nuclear lamina strain states revealed by intermolecular force biosensor

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.