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Development of highly sensitive biological barrier evaluation method using cellular pH perturbation phenomenon and field-effect transistor

Research Project

Project/Area Number 19K12776
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 InstitutionToyo University (2020-2021)
Tokyo Medical and Dental University (2019)

Principal Investigator

Goda Tatsuro  東洋大学, 理工学部, 教授 (20588347)

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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordspH摂動 / タイトジャンクション / 上皮バリア / 生体バリア透過 / 高分子ナノキャリア / バイオトランジスタ / pH摂動 / 組織工学 / 上皮細胞 / バイオセンサ / トランジスタ / バイオ界面 / 生体バリア / 細胞膜 / 薬剤キャリア / 細胞アッセイ
Outline of Research at the Start

独自に開発した細胞非侵襲的なpH摂動操作と電気的イオンセンシング法を用いて、「究極的な高感度」と「高スループット」を実現する細胞膜および上皮タイトジャンクション(TJ)の生体バリアに対するIn vitro評価法を開発する。本手法の有用性を示すために、1.機能性ナノ材料の細胞膜透過性機構の解明、2.上皮TJを標的とする薬剤評価技術の確立、に取り組む。期待成果として、高効率な薬物送達系キャリア分子開発に向けた評価技術の確立や、TJ標的型新規薬剤開発の促進、培養細胞アレイ/培養組織を用いた高スループット薬剤スクリーニング、がん浸潤・転移時の組織物理化学的環境変化の非侵襲計測等が挙げられる。

Outline of Final Research Achievements

Evaluation of barrier properties existing in the living body such as cell membranes and epithelial tight junction (TJ) is an important research subject such as physiological functions and development of biomedical engineering nanomaterials. A new technology that allows non-invasive, real-time, multi-parallel, sensitive, and real-time measurements is required to overcome issues of existing assays for biomembrane injuries and tight junction breaches. In this study, we have recently succeeded in developing an original method that can evaluate biological barrier properties with sensitivity and selectivity that cannot be achieved by conventional methods, using induced pH perturbations. In the future, the new assay developed can be applied both in life science and biomedical engineering.

Academic Significance and Societal Importance of the Research Achievements

細胞膜やTJといった生体バリア評価の重要性は増しつつある。本研究では、細胞膜障害性やTJ破綻の評価に原理証明実験に取り組み、pH摂動法が真に有効な技術であることを検証できた。今後、本測定系は、がん浸潤・転移時の組織透過性の非侵襲計測といった基礎学問と、TJ標的型新規薬剤開発の促進や高スループット薬剤スクリーニング、高効率かつ安全なドラッグデリバリーナノキャリアの開発といった産業応用双方の観点から、数多くの波及効果が期待される。

Report

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

    (23 results)

All 2022 2021 2020 2019 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results) Presentation (17 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Transepithelial delivery of insulin conjugated with phospholipid-mimicking polymers via biomembrane fusion-mediated transcellular pathways2022

    • Author(s)
      Hatano Hiroaki、Meng Fanlu、Sakata Momoko、Matsumoto Akira、Ishihara Kazuhiko、Miyahara Yuji、Goda Tatsuro
    • Journal Title

      Acta Biomaterialia

      Volume: 140 Pages: 674-685

    • DOI

      10.1016/j.actbio.2021.12.003

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A proton/macromolecule-sensing approach distinguishes changes in biological membrane permeability during polymer/lipid-based nucleic acid delivery2021

    • Author(s)
      Boonstra Eger、Hatano Hiroaki、Miyahara Yuji、Uchida Satoshi、Goda Tatsuro、Cabral Horacio
    • Journal Title

      Journal of Materials Chemistry B

      Volume: 9 Issue: 21 Pages: 4298-4302

    • DOI

      10.1039/d1tb00645b

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Internalization Mechanisms of Pyridinium Sulfobetaine Polymers Evaluated by Induced Protic Perturbations on Cell Surfaces2020

    • Author(s)
      Goda Tatsuro、Hatano Hiroaki、Yamamoto Masaya、Miyahara Yuji、Morimoto Nobuyuki
    • Journal Title

      Langmuir

      Volume: 36 Issue: 33 Pages: 9977-9984

    • DOI

      10.1021/acs.langmuir.0c01816

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phospholipid-mimicking cell-penetrating polymers: principles and applications2020

    • Author(s)
      Goda Tatsuro、Miyahara Yuji、Ishihara Kazuhiko
    • Journal Title

      Journal of Materials Chemistry B

      Volume: 8 Issue: 34 Pages: 7633-7641

    • DOI

      10.1039/d0tb01520b

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Induced Proton Dynamics on Semiconductor Surfaces for Sensing Tight Junction Formation Enhanced by an Extracellular Matrix and Drug2019

    • Author(s)
      Hatano Hiroaki、Goda Tatsuro、Matsumoto Akira、Miyahara Yuji
    • Journal Title

      ACS Sensors

      Volume: 4 Issue: 12 Pages: 3195-3202

    • DOI

      10.1021/acssensors.9b01635

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 再生医療とバイオセンシングの接点2022

    • Author(s)
      合田達郎
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] プロトン漏出法による細胞膜透過性高分子のメカニズム解明2021

    • Author(s)
      合田達郎
    • Organizer
      第50回医用高分子シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] リン脂質模倣両親媒性高分子による上皮バリア透過と物質輸送2021

    • Author(s)
      合田達郎
    • Organizer
      第70回高分子討論会
    • Related Report
      2021 Annual Research Report
  • [Presentation] リン脂質模倣細胞膜透過性ポリマーの展望2021

    • Author(s)
      合田達郎
    • Organizer
      第28回次世代医工学研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 細胞pH摂動の現状と可能性2020

    • Author(s)
      合田達郎
    • Organizer
      第27回次世代医工学研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] リン脂質模倣両親媒性ランダム共重合体の単層上皮細胞シート透過性2020

    • Author(s)
      波多野豊晃, 松元亮, 宮原裕二, 合田達郎
    • Organizer
      第69回高分子討論会
    • Related Report
      2020 Research-status Report
  • [Presentation] pH摂動法による両親媒性リン脂質ポリマーの上皮透過評価2020

    • Author(s)
      波多野豊晃, 松元亮, 宮原裕二, 合田達郎
    • Organizer
      第81回応用物理学会秋季学術講演会
    • Related Report
      2020 Research-status Report
  • [Presentation] 弱酸刺激とpH応答性トランジスタとを組み合わせたpH摂動法によるタイトジャンクション形成評価法の開発2020

    • Author(s)
      波多野豊晃, 合田達郎,松元亮, 宮原裕二
    • Organizer
      令和2年度E部門総合研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] 異なるカチオン構造を持つスルホベタインホモポリマーの細胞取り込みメカニズム評価2020

    • Author(s)
      波多野豊晃,合田達郎,宮原裕二,森本展行,山本雅哉
    • Organizer
      和元年度生体医歯工学共同研究拠点成果報告会
    • Related Report
      2019 Research-status Report
  • [Presentation] Analysis of cellular internalization mechanism of sulfobetaine polymers with different cationic structures2019

    • Author(s)
      Hiroaki Hatano, Tatsuro Goda, Akira Matsumoto, Yuji Miyahara
    • Organizer
      4th International Symposium on Biomedical Engineering
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mechanistic analyses of polymer/lipid-based gene transfection processes through membrane integrity assay using proton sensing tra sistor2019

    • Author(s)
      Eger Boonstra, Hiroaki Hatano, Tatsuro Goda, Satoshi Uchida, Horacio Cabral, Yuji Miyahara
    • Organizer
      4th International Symposium on Biomedical Engineering
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ultrasensitive assays for epithelial tight junction formation by monitoring proton leaks using ISFET2019

    • Author(s)
      Hiroaki Hatano, Tatsuro Goda, Akira Matsumoto, Yuji Miyahara
    • Organizer
      10th International Conference on Molecular Electronics and Bioelectronics (M&BE10)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 機能性表面の構築とバイオセンシング応用2019

    • Author(s)
      合田達郎
    • Organizer
      第68回高分子学会年次大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] pH摂動法を用いたPMB30Wの上皮シート透過性評価2019

    • Author(s)
      波多野豊晃,合田達郎
    • Organizer
      第26回次世代医工学研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 上皮タイトジャンクション形成の新規評価手法の開発2019

    • Author(s)
      波多野豊晃,合田達郎,松元亮,宮原裕二
    • Organizer
      第41回日本バイオマテリアル学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 両親媒性リン脂質ポリマーの上皮細胞バリア透過挙動の解明2019

    • Author(s)
      合田達郎,波多野豊晃,松元亮,石原一彦,宮原裕二
    • Organizer
      第41回日本バイオマテリアル学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] pH摂動法を用いた両親媒性リン脂質ポリマー細胞膜透過機構の解明2019

    • Author(s)
      合田達郎,石原一彦,宮原裕二
    • Organizer
      第68回高分子討論会
    • Related Report
      2019 Research-status Report
  • [Remarks] 合田達郎研究室 東洋大学

    • URL

      http://www2.toyo.ac.jp/~goda/index.html

    • Related Report
      2021 Annual Research Report

URL: 

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

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