Quantification of mechanical interactions between glycolipid membrane and stem cells towards physical understanding of cell adhesion

• Project/Area Number: 16K05515
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological physics/Chemical physics/Soft matter physics
• Research Institution: Kyoto University
• Principal Investigator: Yamamoto Akihisa 京都大学, 高等研究院, 特定助教 (90706805)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ソフトマター物理 / 糖鎖 / 脂質膜 / 力学特性 / 細胞接着 / 生体膜 / 界面相互作用 / 幹細胞 / 中性子散乱

Outline of Final Research Achievements

This research focused on the role of saccharide chains expressed on human embrionic stem cells on their interactions. Dependence of equilibrium inter-membrane distance on the osmotic pressure and calcium ion concentration, and mechanical property of lipid membrane on the molecular structure of saccharide chains and molar ratio were systematically revealed. Adhesion area of human iPS cells on supported lipid membranes functionalized with various kinds of saccharide chains were also measured. The methodology developed in this research was also applied to other systems, resulted in such as revealing long-range lateral correlation of self-assambled domains of fluorocarbon-hydrocarbon molecules, quantification of the interfacial interaction potential between zwitterionic polymer brush and model cells, and the development of bio-marker for quality control and prognosis of human corneal endothelial cells/tissues.

Academic Significance and Societal Importance of the Research Achievements

本研究によってこれまで評価が困難であった糖鎖分子同士の弱い相互作用を、分子間相互作用そのものでなく膜の構造揺らぎという物性を通して非侵襲的な手法で評価する方法論と解析法を確立した。特に幹細胞に特異的なSSEA分子によって膜間相互作用がどのように制御されるかを定量的に明らかにした。実際に生細胞を用いた実験系まで発展させることで、物理的な理解にとどまらず生物学的にも意義深い成果を得た。

Research Products

• [Int'l Joint Research] ハイデルベルク大学(ドイツ)
• [Int'l Joint Research] ストラスブール大学/欧州シンクロトロン放射光施設/ラウエ・ランジェバン研究所(フランス)
• [Int'l Joint Research] ラウエ・ランジュバン研究所/ストラスブール大学/欧州シンクロトロン放射光施設(フランス)
• [Int'l Joint Research] ハイデルベルグ大学(ドイツ)
• [Int'l Joint Research] ハイデルベルグ大学(ドイツ)
• [Int'l Joint Research] ラウエ・ランジェバン研究所/ストラスブルグ大学/欧州シンクロトロン放射光研究所(フランス)
• [Int'l Joint Research] Institut Laue-Langevin(France)
• [Int'l Joint Research] University of Heidelberg(Germany)
• [Journal Article] A Non-Invasive Physical Biomarker for Predictive Diagnosis of In Vitro Cell Sources and Restoring Human Corneal Endothelium (2019)
  • Author(s): Akihisa Yamamoto, Hiroshi Tanaka, Munetoyo Toda, Chie Sotozono, Junji Hamuro, Shigeru Kinoshita, Morio Ueno, and Motomu Tanaka
  • Journal Title: Nature Biomedical Engineering Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Long-Range Lateral Correlation between Self-Assembled Domains of Fluorocarbon-Hydrocarbon Tetrablocks by Quantitative GISAXS (2019)
  • Author(s): Wasim Abuillan, Mariam Veschgini, Salome Mielke, Akihisa Yamamoto, Xianhe Liu, Oleg Konovalov, Marie Pierre Krafft, and Motomu Tanaka
  • Journal Title: ChemPhysChem Volume: 20 Issue: 6 Pages: 898-904
  • DOI: 10.1002/cphc.201800967
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Lensless Tomographic Imaging of Near Surface Structures of Frozen Hydrated Malaria-Infected Human Erythrocytes by Coherent X-Ray Diffraction Microscopy (2017)
  • Author(s): Frank, Viktoria; Chushkin, Yuriy; Froehlich, Benjamin; Abuillan, Wasim; Rieger, Harden; Becker, Alexandra S.; Yamamoto, Akihisa; Rossetti, Fernanda F.; Kaufmann, Stefan、Lanzer, Michael; Zontone, Federico; Tanaka, Motomu
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 1-9
  • DOI: 10.1038/s41598-017-14586-4
  • NAID: 120006540180
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Size, Shape, and Lateral Correlation of Highly Uniform, Mesoscopic, Self-Assembled Domains of Fluorocarbon-Hydrocarbon Diblocks at the Air/Water Interface: A GISAXS Study (2017)
  • Author(s): Veschgini, Mariam; Abuillan, Wasim; Inoue, Shigeto; Yamamoto, Akihisa; Mielke, Salome; Liu, Xianhe; Konovalov, Oleg; Krafft, Marie Pierre; Tanaka, Motomu
  • Journal Title: ChemPhysChem Volume: 18 Issue: 19 Pages: 2791-2798
  • DOI: 10.1002/cphc.201700325
  • Peer Reviewed / Open Access / 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] 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
• [Remarks] Center for Integrative Medicine and Physics
  • URL: https://cimphy.kuias.kyoto-u.ac.jp/
• [Patent(Industrial Property Rights)] 細胞評価方法、細胞評価装置、及び細胞評価プログラム (2018)
  • Inventor(s): 田中（求）、山本、上野、羽室、木下、田中（寛）、戸田、外園
  • Industrial Property Rights Holder: 田中（求）、山本、上野、羽室、木下、田中（寛）、戸田、外園
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
  • Overseas