A Direct Force Probe for Measuring Mechanical Integration Between the Nucleus and the Cytoskeleton

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• The nucleus's mechanical properties are crucial for cellular responses to mechanical forces.
• Understanding nuclear mechanics in living cells requires methods that probe its behavior while connected to the cytoskeleton.

Purpose of the Study:

• To introduce and validate the direct force probe (DFP) as a method for applying force directly to the nucleus in living adherent cells.
• To investigate the mechanical properties of the nucleus and identify cytoskeletal contributions to nuclear force resistance.

Main Methods:

• The direct force probe (DFP) utilizes a micropipette attached to the nuclear surface via suction.
• The micropipette is translated, deforming and translating the nucleus until the restoring force equals the suction force, allowing detachment and elastic relaxation.
• Precise knowledge of suction pressure allows for accurate determination of the force applied to the nuclear surface.

Main Results:

• Nano-scale forces are sufficient to deform and translate the nucleus in living adherent cells.
• Specific cytoskeletal elements were identified as key contributors to the nucleus's ability to resist forces.
• The DFP method allows for the dissection of contributions from both cellular and nuclear components to nuclear mechanical properties.

Conclusions:

• The direct force probe (DFP) is an effective tool for measuring nuclear mechanical properties in living cells.
• The study highlights the significant role of the cytoskeleton in modulating the nucleus's response to mechanical forces.
• DFP enables detailed analysis of the interplay between cellular and nuclear structures under mechanical stress.