Kanazawa University conducts direct measurement of "nuclear elasticity" inside living cells using nanoendoscopy-AFM

A joint research group led by Assistant Professor Takehiko Ichikawa, Researcher Yohei Kono, Associate Professor Takeshi Shimi, and Professor Takeshi Fukuma of the Nano Life Science Institute at Kanazawa University, together with Professor Eishu Hirata of the Cancer Research Institute at Kanazawa University, announced on October 24 that they have succeeded in measuring the elasticity of the nucleus inside living cells and visualizing its distribution using their uniquely developed nanoendoscopy atomic force microscope (nanoendoscopy-AFM). This achievement is expected to lead to new cancer diagnostic techniques based on nuclear stiffness as an indicator. The results were published in ACS Applied Nano Materials on October 12.

The elasticity of cancer cell nuclei is considered a hallmark of malignancy and metastatic potential. However, conventional AFM measures by pressing on the cell membrane, making it impossible to separate the influence of the cell membrane and cytoskeleton. When the nucleus is extracted, it does not reflect the original state of living cells.

The research group developed a technique to apply "nanoendoscopy-AFM" to measure the elasticity of nuclei in human lung cancer cells (PC9). This technique uses an ultrafine needle (nanoneedle probe) with a diameter of 200 nanometers or less, which visualizes internal structures and measures physical properties by scanning them as if piercing them.

Using this technique, the researchers measured PC9 cells under different culture conditions. They found that culturing in serum-free conditions stiffens the nucleus, while adding agents that induce EMT (epithelial-mesenchymal transition), which triggers cancer metastasis, softens the nucleus. Cancer cells may be softening their nuclei to pass through narrow tissue spaces during the process of acquiring metastatic ability.

The results also suggested that nuclear elasticity is caused not by nuclear lamin but by the loosening of chromatin compaction.

Furthermore, this technique can be applied not only to nuclei but also to measuring the nanomechanical properties of other organelles such as mitochondria.

Ichikawa commented: "Previously, it was difficult to measure nuclear elasticity inside living cells due to effects from the cell membrane and other factors. However, this time we succeeded for the first time in the world in directly visualizing the distribution of nuclear stiffness using the 'nanoendoscopy-AFM' technique with an ultrafine needle. We expect that this technology for measuring nuclear elasticity will become a new indicator for future cancer diagnosis."

Journal Information
Publication: ACS Applied Nano Materials
Title: Probing Nanomechanics by Direct Indentation Using Nanoendoscopy-AFM Reveals the Nuclear Elasticity Transition in Cancer Cells
DOI: 10.1021/acsanm.5c03044