Energy Dissipation and Break of Symmetry Caused by Non-Equilibrium Morphological Dynamics of Human Gastric Cancer Cells

• Project Area: Synergy of Fluctuation and Structure:Foundation of Universal Laws in Nonequilibrium Systems
• Project/Area Number: 16H00802
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Kyoto University
• Principal Investigator: 田中 求 京都大学, 高等研究院, 客員教授 (00706814)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
• Keywords: 生命現象の物理 / 細胞の形状揺らぎ / 時空間パターン / 胃腺がん / 形状ゆらぎ / 細胞接着 / 自己駆動型粒子

Outline of Annual Research Achievements

本研究課題では、臨床的にも重要な悪性上皮性腫瘍である胃腺癌の進行・移転という“機能”と形状ゆらぎや運動の時空間パターンとの相関に着目した。当該年度は進行性の高い癌細胞2株について、Eカドヘリンで機能化した表面への接着実験を行った。また、細胞と細胞外基質の接着モデルとして、インテグリンで機能化した表面への接着実験を行った。平均二乗変位を用いて細胞運動を解析し、癌の進行と運動の活発化が定量的に相関することを明らかにした。また、細胞の自発変形をパワースペクトル解析で評価したところ、癌の進行に伴って自発変形によるエネルギー散逸が単調増加することを解明した。これらの結果は癌化に伴い代謝経路が嫌気性の糖代謝に切り替わり多くのエネルギーを消費するというWarburg効果との対応が考えられる。現在論文投稿の準備を進めている。
外部因子（ケモカイン）が細胞の変形と運動に与える影響についての数理モデルとして、太田隆夫（A01班・佐野グループ）と共同研究を行った。太田らの自走粒子の運動方程式に実験で得られた摩擦（移動度）と周期的に変形する力を組み込んだモデルを新たに構築し実験と比較した。変形と運動の非線形カップリング項を考慮することで実験結果を定量的に再現できることを明らかにした(投稿中)。疾患状態にある細胞に化学誘導因子や臨床薬が与える効果をエネルギー散逸のような「動的表現型」とその数理モデルでパターン化するという新しい流れを提案し、発表した(Monzel,.. Tanaka, Scientific Reports (2018))。
一方、この研究で得られた着想をもとに、フッ化炭素直鎖分子の気液界面単分子膜が示す強い非線形粘弾性の解析を行い、その成果を発表した(Mielke,.. Yoshikawa, Krafft, Tanaka, Langmuir (2018)：計画班吉川との共著論文)。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] Heidelberg University/University of Stuttgart(ドイツ)
• [Int'l Joint Research] Institute Curie/European Synchrotron Radiation Facility/University of Strasbourg(フランス)
• [Int'l Joint Research] ハイデルベルグ大学/ビュルツブルグ大学/カールスルーエー大学(ドイツ)
• [Int'l Joint Research] シェフィールド大学(英国)
• [Int'l Joint Research] 欧州放射光施設(ESRF)/マウス臨床研究所(フランス)
• [Int'l Joint Research] コロンビア大学/アイオワ州立大学(米国)
• [Int'l Joint Research] 国立がんセンター(スペイン)
• [Int'l Joint Research]
• [Journal Article] Dynamic cellular phynotyping defines specific mobilization mechanisms of human hematopoietic stem and progenitor cells induced by SDF1α versus synthetic agents. (2018)
  • Author(s): Monzel, C.; Becker, A. S.; Saffrich, R.; Wuchter, P.; Eckstein, V.; Ho, A. D.* & Tanaka, M.*
  • Journal Title: Scientific Reports Volume: 8:1841 Issue: 1 Pages: 1-10
  • DOI: 10.1038/s41598-018-19557-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Emergence of Strong Nonlinear Viscoelastic Response of Semifluorinated Alkane Monolayers. (2018)
  • Author(s): Mielke, S.; Habe, T.; Veschgini, M.; Liu, X.; Yoshikawa, K.; Krafft, M. P. & Tanaka, M.
  • Journal Title: Langmuir Volume: 34 Issue: 7 Pages: 2489-2496
  • DOI: 10.1021/acs.langmuir.7b03997
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dynamic Mechano-Regulation of Myoblast Cells on Supramolecular Hydrogels Cross-Linked by Reversible Host-Guest Interactions (2017)
  • Author(s): Hoerning, Marcel; Nakahata, Masaki; Linke, Philipp; Yamamoto, Akihisa; Veschgini, Mariam; Kaufmann, Stefan; Takashima, Yoshinori; Harada, Akira; Tanaka, Motomu
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 7757-7757
  • DOI: 10.1038/s41598-017-07934-x
  • NAID: 120006366779
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Adsorption of galloyl catechin aggregates significantly modulates membrane mechanics in the absence of biochemical cues. (2017)
  • Author(s): Matsuzaki, T.; Ito, H.; Chevyreva, V.; Makky, A.; Kaufmann, S.; Okano, K.; Kobayashi, N.; Suganuma, M.; Nakabayashi, S.; Yoshikawa, H. Y.* & Tanaka, M.*
  • Journal Title: Phys. Chem. Chem. Phys. Volume: 19 Issue: 30 Pages: 19937-19947
  • DOI: 10.1039/c7cp02771k
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Three-Legged 2,2′-Bipyridine Monomer at the Air/Water Interface: Monolayer Structure and Reactions with Ni(II) Ions from the Subphase (2017)
  • Author(s): Dai, W.; Lee, L.-T.; Schuetz, A.; Zelenay, B.; Zheng, Z.; Borgschulte, A.; Doebeli, M.; Abuillan, W.; Konovalov, O. V.; Tanaka, M.; Schlueter, A. D.
  • Journal Title: Langmuir Volume: 33 Pages: 1646-1654
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mechanical Response of Single Triacylglycerol Spherulites by Using Microcolloidal Probes (2017)
  • Author(s): Yoshikawa, H.Y.; Pink, D. A.; Acevedo, N. C.; Peyronel, F.; Marangoni, A. G.; Tanaka, M.
  • Journal Title: Chemistry Letters Volume: 46 Issue: 4 Pages: 599-601
  • DOI: 10.1246/cl.170014
  • NAID: 130005549063
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ion-Specific Modulation of Interfacial Interaction Potentials between Solid Substrates and Cell-Sized Particles Mediated via Zwitterionic, Super-Hydrophilic Poly(sulfobetaine) Brushes (2017)
  • Author(s): Higaki, Y.; Froehlich, B.; Yamamoto, A.; Murakami, R.; Kaneko, M.; Takahara, A.; Tanaka, M.
  • Journal Title: The Journal of Physical Chemistry B Volume: 121 Issue: 6 Pages: 1396-1404
  • DOI: 10.1021/acs.jpcb.6b11540
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Accumulation of phosphatidylcholine on gut mucosal surface is not dominated by electrostatic interactions. (2017)
  • Author(s): Korytowski, A.; Abuillan, W.; Amadei, F.; Makky, A.; Gumiero, A.; Sinning, I.; Gauss, A.; Stremmel, W.; Tanaka, M.
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Biomembranes Volume: 1859 Issue: 5 Pages: 959-965
  • DOI: 10.1016/j.bbamem.2017.02.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency (2016)
  • Author(s): Frank, V.; Kaufmann, S.; Wright, R.; Horn, P.; Yoshikawa, H. Y.; Wuchter, P.; Madsen, J.; Lewis, A. L.; Armes, S. P.; Ho, A. D.; Tanaka. M.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 24264-24264
  • DOI: 10.1038/srep24264
  • NAID: 120006540181
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tracking mechanical and morphological dynamics of regenerating Hydra tissue fragments using a two fingered micro-robotic hand (2016)
  • Author(s): M. Veschgini, F. Gebert, N. Khangai, H. Ito, R. Suzuki, T. W. Holstein, Y. Mae, T. Arai, and M. Tanaka
  • Journal Title: Applied Physics Letters Volume: 108 Issue: 10 Pages: 1037021-4
  • DOI: 10.1063/1.4943402
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] N-glycosylation enables high lateral mobility of GPI-anchored proteins at a molecular crowding threshold (2016)
  • Author(s): Hartel, A. J. W.; Glogger, M.; Jones, N. G.; Abuillan, W.; Batram, C.; Hermann, A.; Fenz, S. F.; Tanaka, M.; Engstler, M.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 12870-12870
  • DOI: 10.1038/ncomms12870
  • NAID: 120006540182
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High-Resolution Cell Manipulation for Longstanding Load on Red Blood Cells (2016)
  • Author(s): Tsai, C.-H. D.; Horade, M.; Ito, H.; Kaneko, M.; Tanaka, M.
  • Journal Title: IEEE International Conference on Mechatronics and Automation Volume: - Pages: 914-919
  • Peer Reviewed
• [Journal Article] Epidermal-specific deletion of CD44 reveals a function in keratinocytes in response to mechanical stress (2016)
  • Author(s): Shatirishvili, M.; Burk, A. S.; Franz, C. M.; Pace, G.; Kastilan, T.; Breuhahn, K.; Hinterseer, E.; Dierich, A.; Bakiri, L.; Wagner, E. F.; Ponta, H.; Hartmann, T. N.; Tanaka, M.; Orian-Rousseau, V.
  • Journal Title: Cell Death and Disease Volume: 7 Issue: 11 Pages: e2461-e2461
  • DOI: 10.1038/cddis.2016.342
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Catch, Load and Launch toward On-Chip Active Cell Evaluation (2016)
  • Author(s): Murakami, R.; Tsai, C.-H. D.; Ito, H.; Tanaka, M.; Sakuma, S.; Arai, F.; Kaneko, M.
  • Journal Title: 2016 IEEE International Conference on Robotics and Automation Volume: - Pages: 1713-1718
  • Peer Reviewed
• [Presentation] Hierarchical Structures and Functions of Interfaces between Bio- and Nonbio-Matter, (2017)
  • Author(s): Motomu Tanaka
  • Organizer: IUMRS-ICAM 2017
  • Int'l Joint Research / Invited
• [Presentation] Symmetry Breaking of Regenerating Hydra Tissues (2017)
  • Author(s): Ryo Suzuki
  • Organizer: International workshop “The diversification of early emerging metazoans: A window into animal evolution?”
  • Int'l Joint Research
• [Presentation] Cancer Progression Alters Morphological Fluctuation and Migration of Human Gastric Cells (2017)
  • Author(s): Akihisa Yamamoto
  • Organizer: Cell Physics 2017
  • Int'l Joint Research
• [Presentation] Cancer Progression Alters Morphological Fluctuation and Self-Propelled Motion of Human Gastric Cells (2017)
  • Author(s): Akihisa Yamamoto
  • Organizer: MIMS workshop “Modeling and Numerical Analysis of Nonlinear Phenomena: Fluid Dynamics, Motion of Interfaces, and Cell Biology”
  • Int'l Joint Research
• [Presentation] Active deformation and symmetry breaking in regenerating Hydra tissues (2017)
  • Author(s): Ryo Suzuki
  • Organizer: MIMS workshop “Modeling and Numerical Analysis of Nonlinear Phenomena: Fluid Dynamics, Motion of Interfaces, and Cell Biology
  • Int'l Joint Research
• [Presentation] 非平衡開放系としての生命 臨床へとつながる医学物理学の開拓 (2017)
  • Author(s): 田中 求
  • Organizer: バイオプラットフォーム研究会 「マイクロロボティクスとバイオの融合シンポジウム」
  • Int'l Joint Research / Invited
• [Presentation] Quantification of biomechanical properties of P.falciparum-infected hemoglobinopathic erythrocytes: Understanding the protective mechanism against severe forms of malaria (2017)
  • Author(s): Benjamin Froehlich
  • Organizer: System Biology of Human Disease
  • Int'l Joint Research
• [Presentation] Nonlinear Viscoelastic Properties of Semifluorinated Alkane Monolayers: an interfacial rheology study (2017)
  • Author(s): Salome Mielke, Xianhe Liu, Marie Pierre Krafft, and Motomu Tanaka
  • Organizer: European Colloid and Interface Science Conference
  • Int'l Joint Research
• [Presentation] In vitro models to investigate the interaction between lipids and mucin: a microinterferometric study (2017)
  • Author(s): Federico Amadei and Motomu Tanaka
  • Organizer: European Colloid and Interface Science Conference
  • Int'l Joint Research
• [Presentation] Quantification of Morphological Dynamics and Symmetry Break in Regenerating Hydra Tissues (2016)
  • Author(s): Ryo Suzuki
  • Organizer: The 54th Annual Meeting of the Biophysical Society of Japan
  • Place of Presentation: Tsukuba, Japan
  • Year and Date: 2016-11-25
  • Int'l Joint Research
• [Presentation] Experimental investigation of polar pattern formation in driven filament systems through collisions (2016)
  • Author(s): Ryo Suzuki
  • Organizer: International Symposium: Current and Future Perspectives in Active Matter
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2016-10-28
  • Int'l Joint Research / Invited
• [Presentation] Spatio-temporal patterns in migrating cells: towards physical diagnosis of human diseases (2016)
  • Author(s): Motomu Tanaka
  • Organizer: Gordon Research Conference Biointerface Sciences
  • Place of Presentation: Les Diablerets, Switzerland
  • Year and Date: 2016-06-12
  • Int'l Joint Research / Invited
• [Patent(Industrial Property Rights)] 培地用高分子ゲル、培地、細胞の培養方法及びキット (2016)
  • Inventor(s): 原田明、高島義徳、中畑雅樹、田中求、ホールニング・マルセル
  • Industrial Property Rights Holder: 原田明、高島義徳、中畑雅樹、田中求、ホールニング・マルセル
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-07-28
• [Patent(Industrial Property Rights)] 検出方法及びデバイス (2016)
  • Inventor(s): 上野祐子、古川一暁、手島哲彦、田中求
  • Industrial Property Rights Holder: 上野祐子、古川一暁、手島哲彦、田中求
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-10-28