Development of a technique to dynamically control myotube formation using wrinkle substrates with reversibly switchable topography

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K12781
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Kyoto University
• Principal Investigator: Suzuki Ryo 京都大学, 高等研究院, 特定助教 (10768071)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 筋管形成 / 細胞接着誘導 / 方向秩序

Outline of Final Research Achievements

How cells respond to dynamical changes of the extracellular cellular matrix is important for the homeostasis of cellular tissues. Using wrinkle substrates where surface topography can be modified, we studied the influence of topography on myotube formation by quantitative analysis of gain/loss of myotube formation capability and developed a technique to dynamically regulate myotube formation.
Here, we found that on wrinkle substrates (1) myotube formation capability was enhanced for wild-type cells, via quantitative analysis of physical readouts such as shape and directional order parameter of cell populations and (2) PIEZO1 knock-out cells, that typically do not form myotubes, could form myotubes. Also, dynamically changing the wrinkle direction during the myotube formation process, we discovered that in the early phases of myotube formation, cells created myotubes in the new wrinkle direction while in the latter stages, cells did not respond to the change in wrinkle direction.

Free Research Field

生物物理

Academic Significance and Societal Importance of the Research Achievements

細胞外基質による細胞制御は細胞接触誘導と呼ばれ、様々な凹凸構造基板を用いた細胞応答の研究は数多く報告されてきた。しかし、多くは凹凸構造の方向や波長を変えられない静的な基板を用いたものに限られており、組織における機能と微小環境構造変化の関係性の本質に切り込めていなかった。そのため、本研究で得られた成果は学術的に非常に重要である。
また社会的意義として、本研究で扱った既存のトポグラフィを改めて変えるといった本来自然界で行われている環境構造の動的変化は発生や疾患の過程で生じる細胞外基質の動的な変化に対する細胞応答の理解にも展開可能であり、筋管形成に限らず様々な系の動的制御技術に応用が期待できる。