Elucidation of anterior-posterior polarity creation mechanism of migrating cells using artificial cell manipulation

2020 Fiscal Year Final Research Report

• Project/Area Number: 17KT0110
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Constructive Systems Biology
• Research Institution: Yamaguchi University
• Principal Investigator: Iwadate Yoshiaki 山口大学, 大学院創成科学研究科, 准教授 (40298170)
• Project Period (FY): 2017-07-18 – 2021-03-31
• Keywords: アメーバ運動 / 細胞運動 / ミオシン / アクチン

Outline of Final Research Achievements

Keratocytes migrate while maintaining their shape with a vast crescent-shaped lamellipodium in front of the spindle-shaped cell body. In a migrating keratocyte, stress fibers, which are bundles of actomyosin, are always arranged perpendicular to the migration direction of the cell. In this study, we investigated the mechanism by which cells sense mechanical stimuli such as the rigidity of substrate and generate the anterior-posterior polarity of cells by the function of actomyosin. Artificial destruction of the stress fibers in keratocytes resulted in unstable anterior-posterior polarity of the cells. In addition, when Amoeba proteus cells, which are completely different from keratocytes, are dispersed on an elastic substrate and the elastic substrate is repeatedly stretched in order to give a mechanical stimulus from the substrate, the cells retract the pseudopodia and has anterior-posterior polarity in the direction perpendicular to the stretch.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

オオアメーバが繰り返し基質伸展に応答して前後極性を形成したことから、外部からの機械的刺激に応答して前後極性を形成させるメカニズムは、ケラトサイトにとどまらない普遍的な前後極性形成メカニズムであることがわかった。さらに、オオアメーバが外部からの機械的な刺激に対して前後極性を形成させる時に、ストレスファイバ（アクトミオシン）の自律的形成がどのように起きるか検討している。本研究をさらに発展させれば、化学的な試薬を用いない非侵襲な方法で、細胞の移動方向の制御が可能になる。これはがん転移の制御や、傷跡の残らない傷修復など新しい医療応用に発展する可能性を持つ。