Probing Nanomechanics by Direct Indentation Using Nanoendoscopy-AFM Reveals the Nuclear Elasticity Transition in...

Area of Science:

• Biophysics
• Cell Biology
• Cancer Research

Background:

• Nuclear structural changes, including elasticity, are potential biomarkers for metastatic cancer.
• Traditional methods for measuring nuclear elasticity have limitations, such as interference from the cell membrane or lack of in-situ assessment.

Purpose of the Study:

• To develop and apply a novel technique, Nanoendoscopy-Atomic Force Microscopy (Nanoendoscopy-AFM), for direct measurement of nuclear elasticity in living cells.
• To investigate the relationship between nuclear elasticity, cellular conditions (serum depletion, TGF-β treatment), and molecular markers (histone modifications, lamins expression).

Main Methods:

• Utilized Nanoendoscopy-AFM to insert a nanoneedle probe directly into living cells for precise nuclear elasticity measurement.
• Mapped the distribution of nuclear elasticity within cells under different experimental conditions.

Main Results:

• Observed an increase in nuclear elasticity under serum depletion.
• Found that TGF-β treatment, inducing epithelial-mesenchymal transition (EMT), decreased nuclear elasticity.
• Demonstrated a positive correlation between nuclear elasticity changes and histone H4 trimethylation at lysine 20, independent of nuclear lamins expression.

Conclusions:

• Nanoendoscopy-AFM provides a direct method to assess nuclear elasticity in intact cells.
• Changes in nuclear elasticity are linked to chromatin structural alterations, specifically histone modifications, during cancer progression.
• Nuclear elasticity serves as a potential biomarker reflecting chromatin state changes relevant to cancer metastasis.