胃癌細胞の非平衡形状ゆらぎのもたらす時空間秩序と転移の相関

• Project Area: Synergy of Fluctuation and Structure:Foundation of Universal Laws in Nonequilibrium Systems
• Project/Area Number: 26103521
• 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, 物質-細胞統合システム拠点, 特定拠点教授 (00706814)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000); Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
• Keywords: 生命現象の物理 / 細胞の形状ゆらぎ / 時空間パターン

Outline of Annual Research Achievements

本研究では、生命現象を動的な非平衡開放系として捉え、細胞を「自己制御する動的システム」 として扱う、という非平衡統計力学からの普遍的アプローチ(アクティブマターの物理)の枠組みの中で、「疾患の物理学」という新分野を開拓する。申請者が確立した"Supported Membrane" という細胞表面の実空間モデルを駆使して、細胞およびその集団の時空間発展や自己秩序化現象を、非平衡物理学の視点から解明してきた。ここででは悪性上皮性腫瘍である胃腺がんに着目する。これまでの2年間で、経代培養が困難なヒト胃腺がん細胞などの実験系を確立し、進行度の浅い細胞株2種についてサロゲート細胞モデル表面との接着面積の形態ダイナミクスと遊走の計測・解析に成功した。究極の目標としては、接着面の形状ゆらぎの時空間パターンとがんの進行の相関を明らかにすることを目指す。

初年度H26年度は経代培養の困難なヒト胃腺がん細胞や、細胞膜の実空間モデルの再構成Eカドヘリンによる機能化といった実験系の確立に集中した。2年目に当たるH27年度に入って進行度の浅い胃腺がん二株について細胞接着面の形状揺らぎと遊走の相関をタイムラプス顕微鏡で追跡することに成功した。タイムラプス機能を顕微鏡に追加することで接着面の形態ダイナミクスをいくつかの細胞で並行に追跡することが可能になり、実験のスループットが格段に向上した。
また、形状揺らぎの解析については昨年度ヒト赤血球を用いて確立した、フーリエ変換した揺らぎ振幅の平均二乗から曲げ弾性やずり弾性といった力学的特性を求める解析手法（Ito, Kuss,... Tanaka, J. Phys. Chem. B (2015) 計画班・市川らとの共著論文）をさらに司法動物ヒドラの組織切片に展開・応用した論文を発表した（Veschgini, Gebert,... Arai, Tanaka, Appl. Phys. Lett. (2016)）。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] University of Heidelberg/Research Center Borstel/Technical University Braunschweig(Germany)
• [Int'l Joint Research] University of Sheffield(英国)
• [Int'l Joint Research] Institut Laue Langevin/European Synchrotron Radiation Facility(France)
• [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] Live cell tracking of symmetry break in actin cytoskeleton triggered by abrupt changes in micromechanical environments (2015)
  • Author(s): S. Inoue, V. Frank, M. Hoerning, S. Kaufmann, H. Y. Yoshikawa, J. P. Madsen, A. L. Lewis, S. P. Armes and M. Tanaka
  • Journal Title: Biomater. Sci. Volume: 3 Issue: 12 Pages: 1539-1544
  • DOI: 10.1039/c5bm00205b
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Quantification of the Influence of Endotoxins on the Mechanics of Adult and Neonatal Red Blood Cells (2015)
  • Author(s): Hiroaki Ito, Navina Kuss, Bastian E. Rapp, Masatoshi Ichikawa, Thomas Gutsmann, Klaus Brandenburg, Johannes M. B. Poeschl, and Motomu Tanaka
  • Journal Title: The Journal of Physical Chemistry B Volume: 119 Issue: 25 Pages: 7837-7845
  • DOI: 10.1021/acs.jpcb.5b01544
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Fine Adjustment of Interfacial Potential between pH-Responsive Hydrogels and Cell-Sized Particles (2015)
  • Author(s): Cornelia Monzel, Mariam Veschgini, Jeppe Madsen, Andrew L. Lewis, Steven P. Armes, and Motomu Tanaka
  • Journal Title: Langmuir Volume: 31 Issue: 31 Pages: 8689-8696
  • DOI: 10.1021/acs.langmuir.5b01896
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Bacterial lipopolysaccharides form physically cross-linked, two-dimensional gels in the presence of divalent cations (2015)
  • Author(s): Moritz Herrmann, Emanuel Schneck, Thomas Gutsmann, Klaus Brandenburgb and Motomu Tanaka
  • Journal Title: Soft Matter Volume: 11 Issue: 30 Pages: 6037-6044
  • DOI: 10.1039/c5sm01002k
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Influence of length and conformation of saccharide head groups on the mechanics of glycolipid membranes: Unraveled by off-specular neutron scattering (2015)
  • Author(s): Akihisa Yamamoto, Wasim Abuillan, Alexandra S. Burk, Alexander Koerner, Annika Ries, Daniel B. Werz, Bruno Deme, and Motomu Tanaka
  • Journal Title: The Journal of Chemical Physics Volume: 142 Issue: 15 Pages: 154907-154907
  • DOI: 10.1063/1.4918585
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Impact of Lipid Oxidization on Vertical Structures and Electrostatics of Phospholipid Monolayers Revealed by Combination of Specular X‐ray Reflectivity and Grazing-Incidence X‐ray Fluorescence (2015)
  • Author(s): Agatha Korytowski, Wasim Abuillan, Ali Makky, Oleg Konovalov, and Motomu Tanaka
  • Journal Title: The Journal of Physical Chemistry B Volume: 119 Issue: 30 Pages: 9787-9794
  • DOI: 10.1021/acs.jpcb.5b04451
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Impact of Lipid Oxidization on Biophysical Properties of Model Cell Membranes (2015)
  • Author(s): Ali Makky, and Motomu Tanaka
  • Journal Title: The Journal of Physical Chemistry B Volume: 119 Issue: 18 Pages: 5857-5863
  • DOI: 10.1021/jp512339m
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Cytoadhesion of P. falciparum-infected erythrocytes to chondroitin-4-sulfate is cooperative and shear-enhanced (2015)
  • Author(s): Harden Rieger, Hiroshi Y. Yoshikawa, Katharina Quadt, Morten A. Nielsen, Cecilia P. Sanchez, Ali Salanti, Motomu Tanaka and Michael Lanzer
  • Journal Title: Blood Volume: 125(2) Issue: 2 Pages: 383-391
  • DOI: 10.1182/blood-2014-03-561019
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] High Precision, Electrochemical Detection of Reversible Binding of Recombinant Proteins on Wide Bandgap GaN Electrodes Functionalized with Biomembrane Models (2014)
  • Author(s): Nataliya Frenkel, Jens Wallys, Sara Lippert, Joerg Teubert, Stefan Kaufmann, Aparna Das, Eva Monroy Martin Eickhoff and Motomu Tanaka
  • Journal Title: Adv. Funct. Mater Volume: 24 Issue: 31 Pages: 4927-4934
  • DOI: 10.1002/adfm.201400388
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Counteracting the inhibitory effect of proteins towards lung surfactant substitutes: a fluorocarbon gas helps displace albumin at the air/water interface (2014)
  • Author(s): Phuc Nghia Nguyen, Mariam Veschgini, Motomu Tanaka, Gilles Waton, Thierry Vandammec and Marie Pierre Krafft
  • Journal Title: Chem. Commun. Volume: 50 Issue: 78 Pages: 11576-11579
  • DOI: 10.1039/c3cc47840h
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mechanistic Investigation of Interactions between Steroidal Saponin Digitonin and Cell Membrane Models (2014)
  • Author(s): Nataliya Frenkel, Ali Makky, Ikhwan Resmala Sudji,Michael Wink, and Motomu Tanaka
  • Journal Title: J. Phys. Chem. B Volume: 118 Issue: 50 Pages: 14632-14639
  • DOI: 10.1021/jp5074939
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Active Deformation and Motion of Biological Matter: Beyond Toy Models (2016)
  • Author(s): Motomu Tanaka
  • Organizer: 生体工学・生物模倣技術に関するセミナー
  • Place of Presentation: Tsukuba
  • Year and Date: 2016-03-08
  • Invited
• [Presentation] 臨床医学と物理学の出会い: 疾患の物理学 (2016)
  • Author(s): Motomu Tanaka
  • Organizer: 物理学は生物現象の謎を解けるか（基礎生物学研究会）
  • Place of Presentation: Okazaki
  • Year and Date: 2016-01-05
  • Invited
• [Presentation] Spatio-Temporal Patterns of Migrating Cells Tracked on Supported Membranes (2015)
  • Author(s): Motomu Tanaka
  • Organizer: Tethered Membrane 2015 International Conference
  • Place of Presentation: Singapore
  • Year and Date: 2015-11-08
  • Int'l Joint Research / Invited
• [Presentation] Modeling Active Deformation and Motion of Biological Matter – Beyond Toy Models, Towards Cells and Tissues, (2015)
  • Author(s): Motomu Tanaka
  • Organizer: JST Forum “Mathematics for 22nd Century”
  • Place of Presentation: Tokyo
  • Year and Date: 2015-09-28
  • Int'l Joint Research / Invited
• [Presentation] Morphological Dynamics and Adhesion of Cells in Human Diseases (2015)
  • Author(s): Motomu Tanaka
  • Organizer: EMBO Conference “Physics of Cells”
  • Place of Presentation: Lichtenfels, Germany
  • Year and Date: 2015-07-01
  • Int'l Joint Research / Invited
• [Presentation] Physics of Carbohydrates at Biological Interfaces (2015)
  • Author(s): Motomu Tanaka
  • Organizer: 76th Gifu Glycoscience Lecture
  • Place of Presentation: Gifu
  • Year and Date: 2015-06-29
  • Invited
• [Presentation] 刺激応答性材料を用いたヒト幹細胞の動的制御 (2015)
  • Author(s): Motomu Tanaka
  • Organizer: 新学術領域 「ゆらぎと構造」＋「分子ロボティクス」合同研究会
  • Place of Presentation: Tokyo
  • Year and Date: 2015-06-27
  • Invited
• [Presentation] Physics of Sugars at Interfaces: Electrostatistics, Mechanics to Biological Functions (2015)
  • Author(s): Motomu Tanaka
  • Organizer: Hierarchical Structures and Dynamics at Soft Interfaces – from surfactants, cells to peacock’s train
  • Place of Presentation: Kyoto
  • Year and Date: 2015-05-16
• [Presentation] Life as Open Non-Equilibrium Systems (1, 2) (2015)
  • Author(s): Motomu Tanaka
  • Organizer: Kyoto Winter School for Statistical Mechanics, Frontiers in Statistical Mechanics: From Nonequilibrium Fluctuations to Active Matter
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-02-04 – 2015-02-17
  • Invited
• [Presentation] 統計物理学と臨床医学 (2015)
  • Author(s): 田中 求
  • Organizer: 革新的バイオマーカー創出と臨床応用講演会
  • Place of Presentation: 大阪
  • Year and Date: 2015-01-30
  • Invited
• [Presentation] Grazing Incidence X-Ray Diffraction and Scattering on Liquid Surfaces (2014)
  • Author(s): Motomu Tanaka
  • Organizer: Creation of Bio-Inspired, Non-Biological Mesoscale Hybrid Materials
  • Place of Presentation: Kyoto Japan
  • Year and Date: 2014-11-18 – 2014-11-19
• [Presentation] Extracting Information Behind Stochastic Cell Dynamics: What shape and Motion Talk (2014)
  • Author(s): 田中 求
  • Organizer: Japanese-German Mini-Symposium on "Quantitative Tools for the Analysis of Cancer Microenvironments
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 2014-10-24
• [Presentation] Quantifying Physical Quantities from Soft, Buried Interfaces 埋もれたソフト界面の物理の定量評価 (2014)
  • Author(s): 山本 暁久
  • Organizer: 第63回高分子討論会
  • Place of Presentation: 長崎
  • Year and Date: 2014-09-24 – 2014-09-26
  • Invited
• [Presentation] Stochastic Morphological Dynamics in Cancer (2014)
  • Author(s): 田中 求
  • Organizer: 新学術領域「ゆらぎと構造の協奏」第2回領域会議
  • Place of Presentation: 札幌市
  • Year and Date: 2014-08-30 – 2014-08-31
• [Presentation] What Shape and Motion Talk: Statistical Physics Meets Cancer (2014)
  • Author(s): Motomu Tanaka
  • Organizer: 8th IUPAP International Conference on Biological Physics
  • Place of Presentation: Beijing, China
  • Year and Date: 2014-06-18 – 2014-06-22
  • Invited
• [Presentation] Grazing Incidence X-Ray Diffraction and Scattering on Liquid Surfaces (2014)
  • Author(s): Motomu Tanaka
  • Organizer: International Symposium on Synthetic Two-Dimensional Polymers
  • Place of Presentation: Zurich, Swizerland
  • Year and Date: 2014-06-02 – 2014-06-03
  • Invited
• [Presentation] 胃癌細胞の非平衡形状ゆらぎのもたらす時空間秩序と転移の相関 (2014)
  • Author(s): 山本 暁久
  • Organizer: 新学術領域研究「ゆらぎと構造の協奏」公募班キックオフ研究会
  • Place of Presentation: 京都
  • Year and Date: 2014-04-26 – 2014-04-27