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Developments of measuring nanomechanical dynamics of a fragile cell surface by scanning ion conductance microscopy

Research Project

Project/Area Number 21H01821
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 29030:Applied condensed matter physics-related
Research InstitutionKanazawa University

Principal Investigator

Shinji Watanabe  金沢大学, ナノ生命科学研究所, 准教授 (70455864)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2023: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2022: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2021: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Keywords細胞計測 / 走査型プローブ顕微鏡 / 走査型イオン伝導顕微鏡 / 生細胞計測 / ナノメカニクス / メカノバイオロジー / 生細胞イメージング / 細胞力学 / 生細胞 / イオン伝導顕微鏡 / ナノピペット / 走査プローブ顕微鏡
Outline of Research at the Start

細胞が創発する力学挙動を物理計測により理解し、細胞機能の解明を目指す取り組みが近年積極的に行われている。しかし既存技術では、僅かな力で損傷する脆弱な細胞の力学特性を精密に計測することや、非常に弱い力に応答する細胞の力学特性を探ることが困難であった。そこで本研究では、申請者がこれまで独自に発展させてきた走査プローブ顕微鏡技術を基盤に、既存技術の100分の1程度の力で細胞力学特性を計測する技術を開発する。この技術を用いて、これまで見落とされてきた極めて弱い力に応答する細胞表層のナノ構造の検出や、それらの局所弾性率の定量および時空間動態を計測可能な技術を確立する。

Outline of Final Research Achievements

In this study, we developed a technique for simultaneously measuring the topography and elasticity of cell surfaces with high spatiotemporal resolution using Scanning Ion Conductance Microscopy (SICM). We applied this technique to eight types of cancer cells with systematically varying malignancies. Our findings indicate that SICM data, such as surface roughness, motility, and elasticity, can effectively classify these eight types of cancer cells. Furthermore, we established a system for long-term SICM measurement of 3D-cultured organoids, successfully tracking the temporal changes in shape and elasticity of individual cells within the organoids.

Academic Significance and Societal Importance of the Research Achievements

既存技術では計測困難である生きた細胞表層のナノ形状や力学動態を長時間にわたって低侵襲かつ高時空間分解能で可視化する技術をSICMを用いて開発した。2次元培養した単一細胞に対する計測だけでなく3次元培養したオルガノイドといった背の高い組織様の多細胞もSICMにより長時間計測可能な測定系を構築した。SICMで計測した細胞表層ナノ形状・ナノ力学動態といった細胞表層情報より、細胞の生理状態を分類する手段の可能性を見出した。走査型プローブ顕微鏡では、通常アクセスが困難な生きた細胞の基底面のナノ構造・力学動態を可視化することも成功した。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (41 results)

All 2024 2023 2022 2021

All Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (34 results) (of which Int'l Joint Research: 6 results,  Invited: 7 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Molecular Scale Structure and Kinetics of Layer-by-Layer Peptide Self-Organization at Atomically Flat Solid Surfaces2023

    • Author(s)
      Yurtsever Ayhan、Sun Linhao、Hirata Kaito、Fukuma Takeshi、Rath Siddharth、Zareie Hadi、Watanabe Shinji、Sarikaya Mehmet
    • Journal Title

      ACS Nano

      Volume: 17 Issue: 8 Pages: 7311-7325

    • DOI

      10.1021/acsnano.2c10673

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mapping Nanomechanical Properties of Basal Surfaces in Metastatic Intestinal 3D Living Organoids with High‐Speed Scanning Ion Conductance Microscopy2022

    • Author(s)
      Wang Dong、Nguyen Han Gia、Nakayama Mizuho、Oshima Hiroko、Sun Linhao、Oshima Masanobu、Watanabe Shinji
    • Journal Title

      Small

      Volume: 19 Issue: 9 Pages: 2206213-2206213

    • DOI

      10.1002/smll.202206213

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Situ Visualization of Dynamic Cellular Effects of Phospholipid Nanoparticles via High‐Speed Scanning Ion Conductance Microscopy2022

    • Author(s)
      Kenry、Sun Linhao、Yeo Trifanny、Middha Eshu、Gao Yuji、Lim Chwee Teck、Watanabe Shinji、Liu Bin
    • Journal Title

      Small

      Volume: 18 Issue: 37 Pages: 2203285-2203285

    • DOI

      10.1002/smll.202203285

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nano-scale physical properties characteristic to intestinal cancer cells identified by high speed-scanning ion conductance microscope2022

    • Author(s)
      D. Wang, L. Sun, S. Okuda, D. Yamamoto, M. Nakayama, H. Oshima, H. Saito, Y. Kouyama, K. Mimori, T. Ando, S. Watanabe, M. Oshima
    • Journal Title

      Biomaterials

      Volume: 280 Pages: 121256-121256

    • DOI

      10.1016/j.biomaterials.2021.121256

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recent advances in the glass pipet: from fundament to applications.2022

    • Author(s)
      Y. Zhou, L. Sun, S. Watanabe, T. Ando
    • Journal Title

      Anal. Chem.

      Volume: 94 Issue: 1 Pages: 324-335

    • DOI

      10.1021/acs.analchem.1c04462

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Nanopipette-based nanthermal atmospheric pressure pplasma for individual cell stimulation2024

    • Author(s)
      Han Gia Ngyuyen, Linhao SUn, Shinya Kumagai, Shinji Watanabe
    • Organizer
      2023年度日本生物物理学会中部支部会討論会
    • Related Report
      2023 Annual Research Report
  • [Presentation] SICM高速化のための容量性ノイズの低減2024

    • Author(s)
      亀井翔天, 渡邉信嗣
    • Organizer
      2023年度日本生物物理学会中部支部会討論会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 高速広域走査型イオン伝導顕微鏡に向けた走査機構と制御技術の開発2024

    • Author(s)
      宮下和己, 渡邉信嗣
    • Organizer
      SPM研究会2023
    • Related Report
      2023 Annual Research Report
  • [Presentation] SICM計測における容量性ノイズと適切な微小電流検出器のコンポーネントの検討2024

    • Author(s)
      亀井翔天, 渡邉信嗣
    • Organizer
      SPM研究会2023
    • Related Report
      2023 Annual Research Report
  • [Presentation] Scanning Ion Conductance Microscopy for Time-Resolved Nanomechanical Mapping of Living Cells2023

    • Author(s)
      Shinji Watanabe
    • Organizer
      31st International Colloquium on Scanning Probe Microscopy (ICSPM31)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 高速走査型イオン伝導顕微鏡による細胞計測と技術課題2023

    • Author(s)
      渡邉 信嗣
    • Organizer
      ~ SPM で拓くナノスケールの世界~ 走査型プローブ顕微鏡セミナー
    • Related Report
      2023 Annual Research Report
  • [Presentation] Investigation of cell membrane exposed to nanopipette-based non-thermal atmospheric pressure plasma using scanning probe microscope2023

    • Author(s)
      Nguyen Han Gia, Sun Linhao, Kumagai Shinya, Watanabe Shinji
    • Organizer
      第61回日本生物物理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Current noise reduction of scanning ion conductance microscopy for visualizing structural dynamics of living cell membranes2023

    • Author(s)
      Shoma Kamei, Shinji Watanabe
    • Organizer
      第61回日本生物物理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Time-Resolved Imaging of Nanomechanics and Nanostructures of Living Cells with Scanning Ion Conductance Microscopy2023

    • Author(s)
      Shinji Watanabe
    • Organizer
      第7回NanoLSIシンポジウム
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] デジタルフィルタによる低域通過型逆システム構成法を用いたスキャナ応答の改善2023

    • Author(s)
      宮下 和己, 渡邉 信嗣
    • Organizer
      第84回応用物理学秋季学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 広帯域低雑音のSICM計測のための電流アンプの設計とナノピペット容量性ノイズの検討2023

    • Author(s)
      亀井 翔天, 渡邉 信嗣
    • Organizer
      第84回応用物理学秋季学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Combination of nanopipette-based non-thermal atmospheric pressure plasma and scanning ion conductance microscopy for investigating plasma-induced modification on cell membrane2023

    • Author(s)
      Han Gia Nguyen, Linhao Sun, Shinya Kumagai, Shinji Watanabe
    • Organizer
      The First International Symposium of Nano Life Science: Nano Biotechnology
    • Related Report
      2023 Annual Research Report
  • [Presentation] A Lab-made Transmission Electron Microscopy Holder Specially Designed for Evaluating Probes of Pipettes-based Scanning Probe Microscopy2023

    • Author(s)
      Hirotoshi Furusho, Han Gia Nguyen, Shoma Kamei, Linhao Sun, Shinji Watanabe, Takeshi Fukuma
    • Organizer
      第79回日本顕微鏡学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 高速SICMのための超低雑音広帯域トランスインピーダンスアンプの開発2023

    • Author(s)
      亀井 翔天, 渡邉 信嗣
    • Organizer
      第70回応用物理学会春季学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] モデル誤差補償器による高速制御のためのスキャナ制御の検討2023

    • Author(s)
      宮下 和己, 金田 駿哉, 渡邉 信嗣
    • Organizer
      第70回応用物理学会春季学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Investigation of plasma effect on cell surface morphology using scanning probe microscopy2023

    • Author(s)
      Nguyen Gia Han, Linhao Sun, Shinya Kumagai, Shinji Watanabe
    • Organizer
      第70回応用物理学会春季学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 高速走査型イオン伝導顕微鏡の開発とその応用2023

    • Author(s)
      渡邉信嗣
    • Organizer
      日本顕微鏡学会バイオSPM研究会2022
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 高速走査型イオン伝導顕微鏡による 生細胞表層ナノ力学動態の可視化2022

    • Author(s)
      渡邉信嗣
    • Organizer
      ナノ科学シンポジウム2022
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] SICMを用いたがん細胞の評価2022

    • Author(s)
      渡邉信嗣
    • Organizer
      ナノプローブテクノロジー第167委員会、第104回研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] High-speed ion conductance microscope to reveal the nanoscale physical properties of metastatic intestinal cancer cells2022

    • Author(s)
      Linhao Sun, Dong Wang, Satoru Okuda, Han G. Nguye, Daisuke Yamamoto, Mizuho Nakayama, Hiroko Oshima, Hideyuki Saito, Yuta Kouyama, Koshi Mimori, Toshio Ando, Shinji Watanabe, Masanobu Oshima
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Nanoscale visualization of cell membrane exposed to non-thermal atmospheric pressure plasma2022

    • Author(s)
      Nguyen Han Gia, Sun Linhao, Kitazaki Tatsuya, Kumagai Shinya, Watanabe Shinji
    • Organizer
      第60回日本生物物理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Nanoscale imaging of plasma-exposed cell membrane using scanning probe microscopy2022

    • Author(s)
      Nguyen Gia Han, Linhao Sun, Tatsuya Kitazaki, Shinya Kumagai, Shinji Watanabe
    • Organizer
      The 83rd JSAP Autumn Meeting 2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] 特徴空間フィルタによる走査型プローブ顕微鏡計測の信号雑音比の改善2022

    • Author(s)
      辰田 貴哉, 渡邉 信嗣
    • Organizer
      2022年第83回応用物理学会秋季学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 帯域増幅機構を用いた逆伝達補償法によるスキャナ応答の改善2022

    • Author(s)
      金田 駿哉, 渡邉 信嗣
    • Organizer
      2022年第83回応用物理学会秋季学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 高速走査プローブ顕微鏡による生きた細菌表層の局所物性イメージング2022

    • Author(s)
      田岡 東, 菊池 洋輔, Sun Linhao, 渡邉 信嗣
    • Organizer
      第18回大腸菌研究会(2022)
    • Related Report
      2022 Annual Research Report
  • [Presentation] 走査型イオン伝導顕微鏡による生きた細菌表層のナノスケール物性およびその動態の観察2022

    • Author(s)
      渡邉 信嗣, Sun Linhao, 菊池 洋輔, 田岡 東
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Elucidation of cell surface topography with plasma irradiation by scanning probe microscopy2022

    • Author(s)
      Nguyen Gia Han, Linhao Sun, Tatsuya Kitazaki, Shinya Kumagai, Shinji Watanabe
    • Organizer
      2022年第69回応用物理学会春季学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Quantitative measurements of the spatial profile of elastic modulus of living cell surface and their dynamics2022

    • Author(s)
      Shinji Watanabe
    • Organizer
      Phys2BioMed winter workshop
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Real-time noise filtering utilized feature space in scanning ion conductance microscopy measurements2021

    • Author(s)
      Yoshiya Tatsuda, Shinji Watanabe
    • Organizer
      29th International Colloquium on Scanning Probe Microscopy
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Improvement in Dynamic Motion in a Hopping-Mode Scanning Ion Conductance Microscopy by a Feedforward- Multiple-Pulse Sequence2021

    • Author(s)
      Shunya Kaneda, Shinji Watanabe
    • Organizer
      29th International Colloquium on Scanning Probe Microscopy
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fine Control of Tip Geometries by Asymmetric Wet Etching for Scanning Ion Conductance Microscopy2021

    • Author(s)
      Riku Yajima, Shinji Watanabe
    • Organizer
      29th International Colloquium on Scanning Probe Microscopy
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 複数遅延半波制御による高速スキャン制御の開発2021

    • Author(s)
      金田 駿哉, 渡邉 信嗣
    • Organizer
      第82回応用物理学会秋季学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 走査型プローブ顕微鏡への機械学習を用いた信号処理アルゴリズムの導入2021

    • Author(s)
      辰田 貴哉, 渡邉 信嗣
    • Organizer
      第82回応用物理学会秋季学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 水酸化カリウムウェットエッチングによるSICM探針の性能改善2021

    • Author(s)
      矢島 陸, 渡辺 信嗣
    • Organizer
      第82回応用物理学会秋季学術講演会
    • Related Report
      2021 Annual Research Report
  • [Book] Chapter:High-speed scanning ion conductance microscopy2024

    • Author(s)
      Linhao Sun, Shinji Watanabe, Toshio Ando
    • Total Pages
      14
    • Publisher
      Elsevier
    • ISBN
      9780124095472
    • Related Report
      2023 Annual Research Report
  • [Patent(Industrial Property Rights)] ガラスピペット及びその製造方法2022

    • Inventor(s)
      矢島陸, 渡邉信嗣
    • Industrial Property Rights Holder
      矢島陸, 渡邉信嗣
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-086767
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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