2018 Fiscal Year Final Research Report
Design of Brownian motor assembly and deciphering the coordinated motion
| Project/Area Number |
17K14375
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biological physics/Chemical physics/Soft matter physics
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Iwaki Mitsuhiro 国立研究開発法人理化学研究所, 生命機能科学研究センター, 上級研究員 (30432503)
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| Research Collaborator |
Kawaguchi Rika
Fujita Keisuke
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | DNAナノテクノロジー / ミオシン / 筋収縮 / 1分子計測 / ブラウニアンラチェット |
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| Outline of Final Research Achievements |
Muscle contraction can be explained by the swinging lever-arm model. However, the dynamic features of how the myosin head swings the lever-arm and its initial interactions with actin are not well understood even though they are essential for the force generation, contraction speed, heat production, and response to mechanical perturbations. This is because myosin heads during force generation have not been directly visualized.
Here, we engineered thick filaments comprising DNA origami and recombinant human muscle myosin, and directly visualized the heads during force generation using nanometer-precision single-molecule imaging. We found that when the head diffuses, it weakly interacts with actin and then strongly binds preferentially to the forward region as a Brownian ratchet. Upon strong binding, the head two-step lever-arm swing dominantly halts at the first step and occasionally reverses direction. These results can explain all mechanical characteristics of muscle contraction.
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| Free Research Field |
生物物理
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| Academic Significance and Societal Importance of the Research Achievements |
多くの生命活動のエネルギー源はアデノシン三リン酸(ATP)であり、その加水分解で得られる自由エネルギー差は、熱ゆらぎ(～kBT)の高々20 倍程度である。そのため、このエネルギーを駆動源にする生体分子は、熱ゆらぎを完全に遮断できず、ある程度の誤作動も許容しながら機能するブラウニアンマシンである。今回、骨格筋や心臓拍動を駆動するブラウニアンマシンであるミオシン集団内の個々の分子動態を世界で初めて直視することに成功した。心臓拍動のメカニズムやミオシンの遺伝的変異を原因とする心筋症の理解、化学的なナノマシン設計への大きな指針を提供することができたと考えている。
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