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A novel mechanism of collective migration of cohesive cells embedded in 3D space

Research Project

Project/Area Number 20K03871
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 13040:Biophysics, chemical physics and soft matter physics-related
Research InstitutionHokkaido University

Principal Investigator

Sato Katsuhiko  北海道大学, 電子科学研究所, 准教授 (90513622)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords細胞の集団運動 / 細胞クラスター移動 / 方向依存的な界面張力 / 細胞表面の一方向流れ / 力学モデル / vertex model / 細胞クラスターの移動 / 3次元空間内での細胞移動 / 力学数理モデル / 収縮力 / 接着力 / 粒子モデル / 方向依存性張力 / 極性 / クラスター / 数理モデル / 細胞間収縮力 / 集団運動 / 形態形成
Outline of Research at the Start

多細胞生物は一つの受精卵からスタートし、細胞分裂を何度も繰り返し、最終的にその形を作り上げる(形態形成)。その形づくりの際に細胞は隣との細胞の接着(クラスター)を保ちながら集団で移動するが、その運動のメカニズムはいまだわかっていない。この問題に物理の力学の視点から挑戦する。3次元空間内で細胞が隣との接着を保ったまま移動するにはどのような条件が必要か、またどのようなメカニズムが可能かを理論と実験の両方の視点から調べる。

Outline of Final Research Achievements

In early development of multicellular organisms, wound healing, and cancer metastasis, cells collectively migrate in three-dimensional tissues, in which cells are confined by a dense extracellular matrix or tightly adhering cells. To clarify the mechanisms of these cell migrations is important not only for natural science but also for medical science. In this study, we approached this problem from a mechanical point of view. By using a cellular vertex model, where forces within the cells are appropriately described, we showed that when cells have polarity and change the strength of contraction force and adhesion force on the cell surface depending on the relative position of the cell surface with respect to the cell center, then the cell surface flows from front to rear. That flow induces cell movement even when cells are adhered to each other to form a cluster. This finding can significantly contribute to our understanding of collective cell migration observed in real experiments.

Academic Significance and Societal Importance of the Research Achievements

細胞の集団運動は多細胞生物の体形成(形態形成)、傷の治癒、病気の転移などで見られる現象であり、そのメカニズムを知ることは自然科学的に重要であるだけでなく、医学的にも重要な課題である。細胞は生体内で組織で囲まれた3次元空間内を複数の細胞が隣の細胞と接着してクラスターを形成したまま移動することができるが、何故、どのように、細胞は隣の細胞と接着したまま移動できるかはこれまで大きな謎であった。本研究では細胞がクラスターを形成したまま移動できる仕組みを力学の視点から提供した。そのメカニズムは現実の世界で観測される多くの複雑な細胞運動の仕組みを解き明かす可能性を持っている。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (10 results)

All 2023 2022 2021 2020

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

  • [Journal Article] Polarized interfacial tension induces collective migration of cells, as a cluster, in a 3D tissue2022

    • Author(s)
      Okuda Satoru、Sato Katsuhiko
    • Journal Title

      Biophysical Journal

      Volume: 121 Issue: 10 Pages: 1856-1867

    • DOI

      10.1016/j.bpj.2022.04.018

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Continuum modeling of non-conservative fluid membrane for simulating long-term cell dynamics2022

    • Author(s)
      Okuda Satoru、Sato Katsuhiko、Hiraiwa Tetsuya
    • Journal Title

      The European Physical Journal E

      Volume: 45 Issue: 8 Pages: 0-0

    • DOI

      10.1140/epje/s10189-022-00223-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Switching of behavioral modes and their modulation by a geometrical cue in the ciliate Stentor coeruleus2022

    • Author(s)
      Echigoya Syun、Sato Katsuhiko、Kishida Osamu、Nakagaki Toshiyuki、Nishigami Yukinori
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 10 Pages: 1021469-1021469

    • DOI

      10.3389/fcell.2022.1021469

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Cell Vertex Model Formulation that Distinguishes the Strength of Contraction Forces and Adhesion at Cell Boundaries2021

    • Author(s)
      Sato Katsuhiko、Umetsu Daiki
    • Journal Title

      Frontiers in Physics

      Volume: 9 Pages: 704878-704878

    • DOI

      10.3389/fphy.2021.704878

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential cell adhesion implemented by Drosophila Toll corrects local distortions of the anterior-posterior compartment boundary2020

    • Author(s)
      Iijima N, Sato K, Kuranaga E, Umetsu D.
    • Journal Title

      Nat Commun.

      Volume: 11 Issue: 1 Pages: 6320-6320

    • DOI

      10.1038/s41467-020-20118-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Cortical Flow Beneath the Plasma Membrane Induces Cluster Cell Migration2023

    • Author(s)
      Katsuhiko Sato
    • Organizer
      Workshop on Recent Trends in Microrheology and Microfluidics
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 対称環境下で現れるクラミドモナスの非対称パターン2022

    • Author(s)
      佐藤勝彦
    • Organizer
      「ジオラマ環境で覚醒する原生知能を定式化する細胞行動力学」 領域会議
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 細胞骨格の流れと基盤との摩擦によって誘起する細胞運動2022

    • Author(s)
      佐藤勝彦
    • Organizer
      日本応用数理学会2022年度年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 対称環境下で現れるクラミドモナスの非対称パターン2022

    • Author(s)
      佐藤勝彦, 飯塚洸介, 神谷律, 若林憲一, 西上幸範, 中垣俊之
    • Organizer
      物理学会2022年秋季大会(物性)
    • Related Report
      2022 Annual Research Report
  • [Presentation] Left-Right Asymmetric Aggregation Patterns of Chlamydomonas under Symmetric Conditions2021

    • Author(s)
      Kosuke Iizuka, Ken-ichi Wakabayashi, Ishikawa Takuji, Ritsu Kamiya, Toshiyuki Nakagaki, Yukinori Nishigami, Katsuhiko Sato
    • Organizer
      The 22nd RIES-Hokudai International Symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2024-01-30  

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