九州大学-研究者情報 [水野大介 (教授) 理学研究院物理学部門]

1.	D. Mizuno, C. Tardin, C. F. Schmidt, and F. C. MacKintosh , Nonequilibrium mechanics of active cytoskeletal networks , Science, 10.1126/science.1134404 , 315 , 5810 , 370-373 , 2007.01, [URL].
2.	D. Mizuno, R. G. Bacabac, C. Tardin, D. Head, C. F. Schmidt, High-resolution probing of cellular force transmission, Physical Review letters, 10.1103/PhysRevLett.102.168102 , 102, 16 , 168102 , 2009.08, [URL].
3.	T. Toyota, D. A. Head, C. F. Schmidt and D. Mizuno , Non-Gaussian athermal fluctuations in active gels, Soft Matter, 10.1039/c0sm00925c , 7, 7 , 3234-3239 , 2011.04, [URL].
4.	Daisuke Mizuno, Suguru Kinoshita, Lara Gay Villaruz, High-frequency affine mechanics and nonaffine relaxation in a model cytoskeleton, PHYSICAL REVIEW E, 10.1103/PhysRevE.89.042711, 89, 4, 2014.04, The cytoskeleton is a network of crosslinked, semiflexible filaments, and it has been suggested that it has properties of a glassy state. Here we employ optical-trap-based microrheology to apply forces to a model cytoskeleton and measure the high-bandwidth response at an anterior point. Simulating the highly nonlinear and anisotropic stress-strain propagation assuming affinity, we found that theoretical predictions for the quasistatic response of semiflexible polymers are only realized at high frequencies inaccessible to conventional rheometers. We give a theoretical basis for determining the frequency when both affinity and quasistaticity are valid, and we discuss with experimental evidence that the relaxations at lower frequencies can be characterized by the experimentally obtained nonaffinity parameter..
5.	Irwin Zaid, Daisuke Mizuno, Analytical Limit Distributions from Random Power-Law Interactions, PHYSICAL REVIEW LETTERS, 10.1103/PhysRevLett.117.030602, 117, 3, 030602-030602, 2016.07, Nature is full of power-law interactions, e.g., gravity, electrostatics, and hydrodynamics. When sources of such fields are randomly distributed in space, the superposed interaction, which is what we observe, is naively expected to follow a Gauss or Levy distribution. Here, we present an analytic expression for the actual distributions that converge to novel limits that are in between these already-known limit distributions, depending on physical parameters, such as the concentration of field sources and the size of the probe used to measure the interactions. By comparing with numerical simulations, the origin of non-Gauss and non-Levy distributions are theoretically articulated..
6.	T. Ariga, M. Tomishige, and D. Mizuno, Nonequilibrium Energetics of Molecular Motor Kinesin, Physical Review Letters, 10.1103/PhysRevLett.121.218101, 121, 218101 , 2018.11, Nonequilibrium energetics of single molecule translational motor kinesin was investigated by measuring heat dissipation from the violation of the fluctuation-response relation of a probe attached to the motor using optical tweezers. The sum of the dissipation and work did not amount to the input free energy change, indicating large hidden dissipation exists. Possible sources of the hidden dissipation were explored by analyzing the Langevin dynamics of the probe, which incorporates the two-state Markov stepper as a kinesin model. We conclude that internal dissipation is dominant..
7.	Kenji Nishizawa, Kei Fujiwara, Masahiro Ikenaga, Nobushige Nakajo, Miho Yanagisawa, Daisuke Mizuno, Universal glass-forming behavior of in vitro and living cytoplasm, SCIENTIFIC REPORTS, 10.1038/s41598-017-14883-y, 7, 1, 15143-15143, 2017.11, Physiological processes in cells are performed efficiently without getting jammed although cytoplasm is highly crowded with various macromolecules. Elucidating the physical machinery is challenging because the interior of a cell is so complex and driven far from equilibrium by metabolic activities. Here, we studied the mechanics of in vitro and living cytoplasm using the particle-tracking and manipulation technique. The molecular crowding effect on cytoplasmic mechanics was selectively studied by preparing simple in vitro models of cytoplasm from which both the metabolism and cytoskeletons were removed. We obtained direct evidence of the cytoplasmic glass transition; a dramatic increase in viscosity upon crowding quantitatively conformed to the super-Arrhenius formula, which is typical for fragile colloidal suspensions close to jamming. Furthermore, the glass-forming behaviors were found to be universally conserved in all the cytoplasm samples that originated from different species and developmental stages; they showed the same tendency for diverging at the macromolecule concentrations relevant for living cells. Notably, such fragile behavior disappeared in metabolically active living cells whose viscosity showed a genuine Arrhenius increase as in typical strong glass formers. Being actively driven by metabolism, the living cytoplasm forms glass that is fundamentally different from that of its non-living counterpart..
8.	Kenji Nishizawa, Marcel Bremerich, Heev Ayade, Christoph F. Schmidt, Takayuki Ariga, Daisuke Mizuno, Feedback-tracking microrheology in living cells, Science Advances, 10.1126/sciadv.1700318, 3, 9, e1700318-e1700318, 2017.09, Living cells are composed of active materials, in which forces are generated by the energy derived from metabolism. Forces and structures self-organize to shape the cell and drive its dynamic functions. Understanding the out-of-equilibrium mechanics is challenging because constituent materials, the cytoskeleton and the cytosol, are extraordinarily heterogeneous, and their physical properties are strongly affected by the internally generated forces. We have analyzed dynamics inside two types of eukaryotic cells, fibroblasts and epithelial-like HeLa cells, with simultaneous active and passive microrheology using laser interferometry and optical trapping technology. We developed a method to track microscopic probes stably in cells in the presence of vigorous cytoplasmic fluctuations, by using smooth three-dimensional (3D) feedback of a piezo-actuated sample stage. To interpret the data, we present a theory that adapts the fluctuation-dissipation theorem (FDT) to out-of-equilibrium systems that are subjected to positional feedback, which introduces an additional nonequilibrium effect. We discuss the interplay between material properties and nonthermal force fluctuations in the living cells that we quantify through the violations of the FDT. In adherent fibroblasts, we observed a well-known polymer network viscoelastic response where the complex shear modulus scales as G* ∝ (-iω)3/4. In the more 3D confluent epithelial cells, we found glassy mechanics with G* ∝ (-iω)1/2 that we attribute to glassy dynamics in the cytosol. The glassy state in living cells shows characteristics that appear distinct from classical glasses and unique to nonequilibrium materials that are activated by molecular motors..
9.	Daisuke Mizuno, Rommel Bacabac, Catherine Tardin, David Head, Christoph F. Schmidt, High-Resolution Probing of Cellular Force Transmission, PHYSICAL REVIEW LETTERS, 10.1103/PhysRevLett.102.168102, 102, 16, 168102-168102, 2009.04, [URL], Cells actively probe mechanical properties of their environment by exerting internally generated forces. The response they encounter profoundly affects their behavior. Here we measure in a simple geometry the forces a cell exerts suspended by two optical traps. Our assay quantifies both the overall force and the fraction of that force transmitted to the environment. Mimicking environments of varying stiffness by adjusting the strength of the traps, we found that the force transmission is highly dependent on external compliance. This suggests a calibration mechanism for cellular mechanosensing..
10.	Daisuke Mizuno, Catherine Tardin, C. F. Schmidt, F. C. MacKintosh, Nonequilibrium mechanics of active cytoskeletal networks, SCIENCE, 10.1126/science.1134404, 315, 5810, 370-373, 2007.01, [URL], Cells both actively generate and sensitively react to forces through their mechanical framework, the cytoskeleton, which is a nonequilibrium composite material including polymers and motor proteins. We measured the dynamics and mechanical properties of a simple three-component model system consisting of myosin II, actin filaments, and cross-linkers. In this system, stresses arising from motor activity controlled the cytoskeletal network mechanics, increasing stiffness by a factor of nearly 100 and qualitatively changing the viscoelastic response of the network in an adenosine triphosphate-dependent manner. We present a quantitative theoretical model connecting the large-scale properties of this active gel to molecular force generation..
11.	N Honda, K Shiraki, F van Esterik, S Inokuchi, H Ebata, D Mizuno, Nonlinear master relation in microscopic mechanical response of semiflexible biopolymer networks, New Journal of Physics, 10.1088/1367-2630/ac6902, 24, 5, 053031-053031, 2022.05, Abstract A network of semiflexible biopolymers, known as the cytoskeleton, and molecular motors play fundamental mechanical roles in cellular activities. The cytoskeletal response to forces generated by molecular motors is profoundly linked to physiological processes. However, owing to the highly nonlinear mechanical properties, the cytoskeletal response on the microscopic level is largely elusive. The aim of this study is to investigate the microscopic mechanical response of semiflexible biopolymer networks by conducting microrheology (MR) experiments. Micrometer-sized colloidal particles, embedded in semiflexible biopolymer networks, were forced beyond the linear regime at a variety of conditions by using feedback-controlled optical trapping. This high-bandwidth MR technology revealed an affine elastic response, which showed stiffening upon local forcing. After scaling the stiffening behaviors, with parameters describing semiflexible networks, a collapse onto a single master curve was observed. The physics underlying the general microscopic response is presented to justify the collapse, and its potentials/implications to elucidate cell mechanics is discussed..

主要総説, 論評, 解説, 書評, 報告書等

全てを見る→

1.	水野大介, 中益朗子, 細胞の力学知覚の物理メカニズム, 2011.04, [URL].
2.	水野大介, 細胞骨格の非平衡揺らぎと力学特性, 2011.04, [URL].

主要学会発表等

全てを見る→

1.	水野大介, 揺動散逸定理を破る生き物の非平衡揺らぎの統計分布, 第69回日本物理学会年次大会シンポジウム「動的ゆらぎの普遍法則」, 2014.03.
2.	Daisuke Mizuno, Levy statistics and dynamics in active cytoskeletons, 2013 SPP Physics Congress, 2013.10.
3.	Daisuke Mizuno, Levy statistics and dynamics in active cytoskeletons, Taiwan International Workshop on Biological Physics and Complex Systems (BioComplex-Taiwan-2013), 2013.07.
4.	水野大介, 揺動散逸定理を破る非平衡揺らぎの時空間構造, 第 17 回久保記念シンポジウム「ゆらぎのなかの構造」, 2012.10.
5.	Daisuke Mizuno, Heev Ayade, Non-Gauss a-thermal fluctuations in active cytoskeletons, Biological & Pharmaceutical Complex Fluids: New Trends in Characterizing Microstructure, Interactions & Properties An ECI Conference, 2012.08.
6.	Daisuke Mizuno, R. G. Bacabac, D.A. Head and Christoph Schmidt, Mechano-sensing and Active Cytoskeleton, inernational symposium on emchanobiology, 2011.11.

学会活動

所属学会名

高分子学会

生物物理学会

細胞生物学会

日本物理学会

学協会役員等への就任

2011.09～2012.09, 九州支部会委員, 九州支部会委員.

学会大会・会議・シンポジウム等における役割

2013.11.30～2013.11.30, 第119回日本物理学会九州支部例会, その他.

2012.12.08～2012.12.08, 第118回日本物理学会九州支部例会, その他.

2013.02.18～2013.02.20, Self-organization and Emergent Dynamics in Active Soft Matter, Other.

2011.12.03～2011.12.03, •第117回日本物理学会九州支部例会, その他.

2012.03.24～2012.03.27, 日本物理学会第67回会年次大会, その他.

2013.02.18～2013.02.20, Self-organization and Emergent Dynamics in Active Soft Matterhtml, Other.

学会誌・雑誌・著書の編集への参加状況

2012.04～2014.03, 日本生物物理学会誌, 国内, 編集　地区委員.

学術論文等の審査

年度	外国語雑誌査読論文数	合計
2015年度	5	5
2015年度	5	5
2014年度	5	5
2013年度	7	7
2012年度	5	5
2011年度	7	7

その他の研究活動

海外渡航状況, 海外での教育研究歴

Goettingen University, Germany, 2007.06～2007.07.

Vrije Universiteit Amsterdam, Netherlands, 2003.04～2006.12.

外国人研究者等の受入れ状況

2015.03～2015.07, Vrije University Amsterdam, Japan, .

2014.04～2014.04, 2週間以上1ヶ月未満, Philippines, 学内資金.

2014.03～2014.04, 2週間以上1ヶ月未満, IPBS/CNRS, France, 学内資金.

2014.02～2015.03, 1ヶ月以上, Vrije University, Netherlands, KNAW.

2015.04～2015.04, 2週間未満, Goettingen University, Germany.

2014.12～2015.02, University of San Carlos, Philippines.

2014.12～2015.02, 1ヶ月以上, Philippines, DOST.

2014.12～2015.05, 1ヶ月以上, Philippines, DOST.

2013.05～2013.05, 1ヶ月以上, 九州大学, China.

2012.04～2012.05, 2週間以上1ヶ月未満, IPBS/CNRS, France, 日本学術振興会.

2012.03～2012.08, 1ヶ月以上, Japan, 日本学術振興会.

2011.08～2011.08, 2週間以上1ヶ月未満, IPBS/CNRS, France, 日本学術振興会.

2010.04～2012.12, 1ヶ月以上, Japan, .

受賞

S.M. Perren Research Award, European Society of Biomechanics, 2006.08.

第４回物理学会若手奨励賞（領域12）, 日本物理学会, 2011.08.

文部科学大臣表彰若手科学者賞, 文部科学省, 2011.04.

研究資金

科学研究費補助金の採択状況(文部科学省、日本学術振興会)

2013年度～2014年度, 基盤研究(C), 細胞集団が形成する組織の非線形・非平衡メカニクスと自発生成力の観測.

2015年度～2017年度, 基盤研究(C), フィードバックマイクロレオロジーによる細胞力学の観測.

2018年度～2020年度, 基盤研究(C), 代謝依存的にガラス形成する細胞質のマイクロレオロジ-.

2020年度～2023年度, 基盤研究(C), 非平衡系のガラス・ジャミング転移.

2020年度～2021年度, 基盤研究(C), 揺動散逸定理の破れと非ガウス性解析に基づく非熱的揺らぎの有用性評価.

2020年度～2021年度, 新学術領域研究, 代表, 揺動散逸定理の破れと非ガウス性解析に基づく非熱的揺らぎの有用性評価.

2020年度～2023年度, 基盤研究(A), 分担, 非平衡系のガラス・ジャミング転移.

2018年度～2020年度, 基盤研究(B), 代表, 代謝依存的にガラス形成する細胞質のマイクロレオロジー.

2015年度～2017年度, 基盤研究(B), 代表, フィードバックマイクロレオロジーによる細胞力学の観測.

2015年度～2016年度, 新学術領域研究, 代表, 力と力学特性による細胞競合メカニズム.

2015年度～2017年度, 新学術領域研究, 「ゆらぎと構造の協奏：非平衡系における普遍法則の確立」のための国際活動支援.

2015年度～2018年度, 基盤研究(C), アクティブなゆらぎ環境下での生体分子モーターキネシンの1分子運動解析.

2015年度～2016年度, 新学術領域研究, 力と力学特性による細胞競合メカニズム.

2013年度～2014年度, 新学術領域研究, 代表, 細胞集団が形成する組織の非線形・非平衡メカニクスと自発生成力の観測.

2013年度～2017年度, 新学術領域研究, 非熱的に駆動されたバイオマターの非平衡動力学.

2012年度～2013年度, 基盤研究(C), 多粒子光トラップによる神経細胞の軸索伸長の制御とその特異性の起源の解明.

2011年度～2012年度, 基盤研究(C), 細胞内部の非平衡力学に基づく非熱的揺動力の計測.

2009年度～2010年度, 基盤研究(C), 生体ソフトマターの非平衡力学計測.

2008年度～2010年度, 基盤研究(C), 生きものの力学物性を支配する非平衡統計力学.

2007年度～2008年度, 基盤研究(C), 細胞内応力分布の高分解能計測による細胞の非平衡動力学の解明.

2003年度～2004年度, 基盤研究(C), 複雑流体中における生体1分子の動的機能計測と、そのマイクロフローシステムへの応用.

2001年度～2002年度, 基盤研究(C), 単一粒子計測による3次元プローブ顕微鏡の開発.

競争的資金(受託研究を含む)の採択状況

2018年度～2018年度, 新分野創成センター先端光科学研究分野プロジェクト, 代表, 補償光学を用いた生体組織の力学計測.

2019年度～2019年度, 新分野創成センター先端光科学研究分野プロジェクト, 代表, フィードバックと補償光学を用いた細胞内粒子の光捕捉操作とレーザー干渉計測.

学内資金・基金等への採択状況

2017年度～2017年度, QRプログラムワカバチャレンジ, 代表, ”活きの良さ”に基づく幹細胞分化と癌悪性化の非平衡力学研究.

九大関連コンテンツ

pure2017年10月2日から、「九州大学研究者情報」を補完するデータベースとして、Elsevier社の「Pure」による研究業績の公開を開始しました。

九州大学知的財産本部「九州大学Seeds集」

QIR　九州大学学術情報リポジトリシステム情報科学研究院

理学部・理学研究院


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