EFFECTS OF MECHANICAL STIMULUS ON BEAT SEQUENCE OF CARDIOMYOCYTES WITH FEEDBACK CONTROL

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K20113
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering and related fields
• Research Institution: Aoyama Gakuin University
• Principal Investigator: Mitsui Toshiyuki 青山学院大学, 理工学部, 教授 (40406814)
• Project Period (FY): 2017-06-30 – 2021-03-31
• Keywords: 心臓 / リズム / 不整脈 / 同期化 / リエントラント / 心筋細胞

Outline of Final Research Achievements

We presented the beat dynamics in sub-mm tissue fragments from atria and ventricles of hearts from chick embryos. The inter-beat intervals and the response to mechanical stimulus are different by the regions. The major finding of this study is synchronization of these fragment pairs physically attached to each other. The probability of achieving this and the time required differ for regional pairs: atrium-atrium, ventricle-ventricle, or atrium-ventricle. Our observation indicates that mechanical stimulus at fragment boundaries induces synchronization. A reentrant-like beat sequence, applicable to testing drugs, is frequently observed during synchronization. To investigate the effects by mechanical stimulus further, we built an instrument applying probe stimuli to cardiac cells. In addition, we successfully added a feedback control to adjust the phase between stimulus and intrinsic beating by fast image processing. This novel instrument shows the phase differences of the responses.

Free Research Field

生物物理、ナノテクノロジー

Academic Significance and Societal Importance of the Research Achievements

胎児期における心臓のメカノセンシングは発生の形状変化において重要と示唆されてきた。我々は組織片ペアの同期化の実験結果において、ペアの接触面における動きが同期化に重要であることを発見した。これは直接的に動きがリズムの安定化に寄与することを示す。また、心房―心室のリエントラント的振る舞いはin vitroの系としてドラッグテスト等への応用が期待できる。次に培養環境下の長期的観測と高速画像処理により構築したフィードバック機構付きの外部刺激装置の完成は筆者の知る限り世界初である。この装置による自律拍動と常時同調した刺激により、発生に近い集団的心筋細胞の形状変化や線維芽細胞の異方的増殖を期待する。