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1995 Fiscal Year Final Research Report Summary

Developmental Research for Peptides Inducing Membrane Fusion between Liposomes and Cells

Research Project

Project/Area Number 06558116
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Biomedical engineering/Biological material science
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

OHKI Kazuo  Tohoku University, Graduate School of Science, Department of Physics, Professor, 大学院・理学研究科, 教授 (80115394)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Toshihide  Tohoku University, Graduate School of Science, Department of Physics, Associate, 大学院・理学研究科, 助教授 (60162004)
OHBA Tetsuhiko  Tohoku University, Graduate School of Science, Department of Physics, Research s, 大学院・理学研究科, 助手 (10250664)
Project Period (FY) 1994 – 1995
Keywordsmembrane fusion / carrier liposome / peptides / DSC / drug delivery system / target cell / phase transition / phospholipids
Research Abstract

Drug delivery system (DDS) is widely studied as a new therapy targeting cells. This research aims to provide peptides that induce membrane fusion between liposomes and a target cell. Differential scanning calorimetry (DSC) is used to detect membrane fusion since mixing of phospholipids accompanied with the fusion is reflected on the thermogram. Melittin, a bee venom peptide, manifested membrane fusion of iposomes between neutral phospholipid and acidic ones through its structure including two separated regions of hydrophobic and basic amino acids. Hemagglutinin is a protein of influenza virus which is responsible for membrane fusion in the process of viral infection. A region composed of 20 amino acids has membrane fusion activity in the hemagglutinin. And, the activity of synthetic peptides that mimic the 20 amino acids are investigated in a liposomal system containing two types of liposomes. One peptide in which glutamic acids are introduced is added to a preparation of phosphatidylcholine liposomes. And the other peptide in which lysines are introduced is added to another preparation of phosphatidylcholine liposomes. When these peptides are used, electrostatic interaction between the liposomes has induced membrane fusion effectively in both gel and fluid phases of liposomal membranes. At pH 5.0, glutamic acids in the peptide are protonated and changed to hydrophobic, and so under this condition effect of hydrophobic interaction on membrane fusion has been investigated. In this case, membrane fusion is much slower compared to the electrostatic case. However, addition of cholesterol to the phosphatidylcholine liposomes raises the rate of membrane fusion induced by hydrophobic interaction.

  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] 安達 智宏: "Interdigitated Structure of Phospholipid-Alcobol System Studied by X-ray diffraction" Biophysical Journal. 68. 1850-1855 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野澤 義則: "生体膜脂質の動的構造と情報交換" 油化学. 44. 721-729 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小林俊秀: "膜脂質の非対称分布" 細胞工学. 14. 1289-1295 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高橋 浩: "Structural and thermotropic Properties of Calcium-Dimyristoyl phosphatidic Acid and Neutral pH Conditions" Biophysical Journal. 69. 1464-1472 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高橋 浩: "Structure and phase behavior of DMPA / (L-poly Lisine) system" Molecular Membrane Biology. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田坂 恭嗣: "Targeted mutagenesis of acyl-lipid desaturases in Synechocystis : Evidence for the important roles of" EMBO Journal. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 遠藤高帆: "A chinese hamster ovary cell mutant resistant to phosphatidylserine is defective in eranebilayer" Experimental Cell Research. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大木和夫: "籏野昌弘監修「新タンパク質応用工学」" フジ・テクノシステム, 950 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Adachi, H,Takahashi, K.Ohki and I.Hatta: "Interdigitated structure of phospholipid-alcohol system studied by X-ray diffraction" Biophys. J.68(5). 1850-1855 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Takahashi, T.Yasue, K.Ohki and I.Hatta: "Strucural and thermotropic properties of calcium-dimyristoyl phosphatidic and complexes at acidic and neutral pH conditions" Biophys. J.69(10). 1464-1472 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Nozawa and K.Ohki: "Dynamic structure and signal transduction of biomembrane lipids (in Japanese)" Oil Chemistry. 44(10). 721-729 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kobayashi, T.Endo and K.Ohki: "Asymmetric distribution of membrane lipids (in Japanese)" Cell Technology. 14(11). 1289-1295 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Endo and K.Ohki: "The construction of lipid asymmetry and its relation to the function in biomembranes (in Japanese)" Exper. Medicine. 14(14). 2070-2074 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Endo and K.Ohki: "Measurements of activities of flippase and endocytosis on a plasma membrane of CHO cells by processing the fluorescence microscopic images (in Japanese)" Membrane. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Takahashi, T.Yasue, K.Ohki and I.Hatta: "Structure and phase behavior of dimyristoylphosphatidic acid/poly (L-lysine) systems" Molecular Membrane Biology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Tasaka, Z.Gombos, Y.Nishiyama, T.Ohba, K.Ohk I and N.Murata: "Targeted mutagenesis of acyl-lipid desaturases in Synechocystis : Evidence for the iportant roles of polyunsaturated membrane lipids in growth, respiration and photosynthesis" EMBO Journal. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Endo, T.Kobayashi and K.Ohki: "A chinese hamster ovary cell mutant resistant to phosphatidylserine is defective in transbilayr movement of cell surface phosphatidylserine" Experimental Cell Research. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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