journal article·2025-10-24Open access

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

Takehiko Ichikawa, Yohei Kono, Makiko Kudo, Takeshi Shimi, Naoyuki Miyashita, Tomohiro Maesaka, Kojiro Ishibashi, Kundan Sivashanmugan, Takeshi Yoshida, Keisuke Miyazawa, Rikinari Hanayama, Eishu Hirata, Kazuki Miyata, Hiroshi Kimura, Takeshi Fukuma

ACS Applied Nano Materials· Volume 8· Issue 42

Abstract

The assessment of nuclear structural changes is considered a potential biomarker of metastatic cancer. However, accurately measuring nuclear elasticity remains challenging. Traditionally, nuclear elasticity has been measured by indenting the cell membrane with a bead-attached atomic force microscopy (AFM) probe or aspirating isolated nuclei with a micropipette tip. However, indentation using a bead-attached probe is influenced by the cell membrane and cytoskeleton, while measurements of isolated nuclei do not reflect their intact state. In this study, we employed Nanoendoscopy-AFM, a technique in which a nanoneedle probe is inserted into a living cell to directly measure nuclear elasticity and map its distribution. Our findings show that nuclear elasticity increases under serum depletion but decreases when serum-depleted cells are treated with TGF-β, which induces epithelial-mesenchymal transition (EMT). Furthermore, we found that changes in nuclear elasticity correlate positively with trimethylation levels of histone H4 at lysine 20, rather than with nuclear lamins expression levels. These findings suggest that alterations in chromatin structure underlie changes in nuclear elasticity during the progression of cancer.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Cellular Mechanics and Interactions · Force Microscopy Techniques and Applications · Nuclear Structure and Function

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan

Division of Electrical Engineering and Computer Science, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan

Division of Tumor Cell Biology and Bioimaging, Cancer Research Institute of Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan

Biochemistry and Molecular Biology, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, Maryland 21201, United States

Department of Immunology, Kanazawa University Graduate School of Medical Sciences, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan

Cell Biology Center, Institute of Integrated Research, Institute of Science Tokyo, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan

Graduate School of Bioscience and Biotechnology, Institute of Science Tokyo, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan

Funding

Ministry of Education, Culture, Sports, Science and Technology · Takeda Medical Research Foundation · Japan Society for the Promotion of Science · Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering · Mitani Foundation for Research and Development · Shimadzu Science Foundation

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