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Development of novel index for metastatic cancer cell evaluation giving mechanical stimuli by kinesin-driven active matrix

Research Project

Project/Area Number 19K12775
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionSaitama University

Principal Investigator

Kawamura Ryuzo  埼玉大学, 理工学研究科, 助教 (50534591)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords運動界面 / がん細胞 / 接着挙動 / 細胞分離技術 / 力学計測 / モータータンパク質 / キネシン / 微小管 / 細胞接着 / 力学刺激 / アクチン細胞骨格 / 細胞分離 / 細胞診断 / 転移性
Outline of Research at the Start

本研究では、細胞スケールの揺らぎ力学刺激を与えることで、がん転移の本質に迫る新しい細胞計測の指標獲得を狙う。独自に開発した『運動界面』では、がん細胞の特異な変形挙動を見いだしている。細胞の変形性から転移能を診断する技術への発展を目指し、運動界面設計の自由度を高めて微小動力学刺激環境がもたらす新しい細胞計測指標を導出する。転移につながる挙動を効果的に顕在化するため、運動界面の動力学設計の最適化 と細胞集団が発する力学揺らぎの計測 を行う。また、力学刺激に応答する細胞群を回収して高転移性がん細胞のモデル株樹立にも挑む。

Outline of Final Research Achievements

An active matrix which was obtained by crosslinking microtubules to a network and driven by kinesin motor proteins decorated on a solid substrate was developed in this research project toward realization of mechanically active matrix to predict metastatic property of cancer cells with expectation to find a new pathological index. The driving property of the active matrix was found to agitate micro-objects actively in isotropic manner and to generate force up to several nanonewtons. In addition to the generation of microscopic fluctuation by the active matrix, micro-fluidic device was established to realize automatic liquid handling and salvage of the cells exposed to mechanical stimuli on the active matrix and separate them according to the adhesion properties in such the dynamic condition. As the active matrix can induce formation of actin aggregations in metastatic cancer cells, this cell analysis method has potential to allow detection of metastatic cancer cells.

Academic Significance and Societal Importance of the Research Achievements

微小管・キネシンをはじめとするモータータンパク質は、細胞運動の根幹を成す分子であり、生物物理学や分子生物学の観点で解明研究が数多く展開されてきたが、運動機能を応用する研究では、分子の小ささに着目した報告がほとんどであった。本研究の手法は架橋した微小管のネットワークでマイクロメートル、ナノニュートンのスケールアップした運動を実現し、有益な応用の道筋として細胞の特徴を動的微小環境下で調べる新しい指標の獲得が期待できるものである。例えば、がん細胞の未知なる転移性を見抜く新技術に発展する可能性を秘めており、医工学的な有益性から社会的意義は大きいと言える。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (8 results)

All 2022 2021 2020 2019

All Journal Article (2 results) (of which Open Access: 1 results,  Peer Reviewed: 1 results) Presentation (6 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results)

  • [Journal Article] Agitation of non-Brownian particles by active matrix of kinesin and microtubule motor proteins2022

    • Author(s)
      Keisuke Meguriya, Tsuyoshi Yokoyama, Naritaka Kobayashi, Hiroshi Y. Yoshikawa, Seiichiro Nakabayashi and Ryuzo Kawamura
    • Journal Title

      ChemRxiv

      Volume: -

    • DOI

      10.26434/chemrxiv-2022-p5xsl

    • Related Report
      2021 Annual Research Report
    • Open Access
  • [Journal Article] Intelligent gels-artificial soft tissue for the next era2021

    • Author(s)
      Ken-Ichi Sano, Ryuzo Kawamura, Yoshihito Osada
    • Journal Title

      Polymer International

      Volume: - Issue: 6 Pages: 616-629

    • DOI

      10.1002/pi.6305

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] 架橋微小管-キネシン運動系の出力計測とその駆動環境との相関2021

    • Author(s)
      辻 成瑛、小林 成貴、中林 誠一郎、吉川 洋史、川村 隆三
    • Organizer
      第59回日本生物物理学会年会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhanced movement of kinesin-driven microtubules by crosslink and the application as active material2021

    • Author(s)
      Ryuzo Kawamura
    • Organizer
      International Workshop on Emergence of Life-Nano-Bio Science
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞骨格タンパク質を利用した動的ゲル材料の開発2020

    • Author(s)
      川村隆三
    • Organizer
      高分子埼玉地区懇話会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Active network of motor proteins as artificial dynamic microenvironment for cells2019

    • Author(s)
      Ryuzo Kawamura, Keisuke Meguriya, Tsuyoshi Yokoyama, Daiki Uehara, Naritaka Kobayashi, Seiichiro Nakabayashi, Hiroshi Y. Yoshikawa
    • Organizer
      ISAGMSM(The 3rd International Symposium for Advanced Gel Materials & Soft Matters)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Kinesin-driven microtubule network for mechanical cellular stimuli2019

    • Author(s)
      Ryuzo Kawamura, Daiki Uehara, Naritaka Kobayashi, Seiichiro Nakabayashi, Hiroshi Yoshikawa
    • Organizer
      NMC2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ATP-fueled active network of microtubules as a dynamic environment for cells2019

    • Author(s)
      Ryuzo Kawamura
    • Organizer
      2nd GLowing Polymer Symposium in KANTO
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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