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Daisuke Mizuno Last modified date:2021.06.07

Professor / material physics
Department of Physics
Faculty of Sciences

Graduate School

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Academic Degree
Country of degree conferring institution (Overseas)
Field of Specialization
biological physics, softmatter, biorheology
Total Priod of education and research career in the foreign country
Outline Activities
research: biological soft matter, nonequilibrium statistical mechanics of life
Research Interests
  • non-equilibrium statistical mechanics of life
    keyword : nonequilibrium mechanics, emergent properties of living systems, complex systems
  • nonequilibrium mechanics and fluctuation in active gels
    exploring the physical calibration mechanism for cellular mechano-sensing
    driven nonequilibrium mechanics in aging colloidal glass
    keyword : microrehology, nanobiology, biomechanics, nonequilibrium statistical mechanics, active gel, cancer, neuron,glycoprotein
Academic Activities
1. 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..
2. K. Nishizawa, K. Fujiwara, M. Ikenaga, N. Nakajo, M. Yanagisawa, and D. Mizuno, Universal glass-forming behavior of in vitro and living cytoplasm, Scientific Reports, 10.1038/s41598-017-14883-y, 7, 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..
3. K. Nishizawa, M. Bremerich, H. Ayade, C. F. Schmidt, T. Ariga and D. Mizuno, Feedback-tracking microrheology in living cells, Science Advances, 10.1126/sciadv.1700318, 3, e1700318, 2017.09.
4. Irwin Zaid, Daisuke Mizuno, Analytical limit distribution from random power-law interactions, Physical Review Letters, 10.1103/PhysRevLett.117.030602, 117, 3, 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..
5. 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..
6. Daisuke Mizuno, Local mechanical response in semiflexible polymer networks subjected to an axisymmetric prestress, PHYSICAL REVIEW E, 10.1103/PhysRevE.88.022717, 88, 2, 2013.08, Analytical and numerical calculations are presented for the mechanical response of fiber networks in a state of axisymmetric prestress, in the limit where geometric nonlinearities such as fiber rotation are negligible. This allows us to focus on the anisotropy deriving purely from the nonlinear force-extension curves of individual fibers. The number of independent elastic coefficients for isotropic, axisymmetric, and fully anisotropic networks are enumerated before deriving expressions for the response to a locally applied force that can be tested against, e.g., microrheology experiments. Localized forces can generate anisotropy away from the point of application, so numerical integration of nonlinear continuum equations is employed to determine the stress field, and induced mechanical anisotropy, at points located directly behind and in front of a force monopole. Results are presented for the wormlike chain model in normalized forms, allowing them to be easily mapped to a range of systems. Finally, the relevance of these findings to naturally occurring systems and directions for future investigation are discussed..
7. N. Nijenhuis, D. Mizuno, J. A. E. Spaan, and C. F. Schmidt, "High-resolution microrheology in the pericellular matrix of prostate cancer cells" , J. Royal Society Interface, 2012.06, Many cells express a membrane-coupled external mechanical layer, the pericellular matrix (PCM), which often contains long-chain polymers. Its role and properties are not entirely known, but its functions are believed to include physical protection, mechanosensing, chemical signalling or lubrication. The viscoelastic response of the PCM, with polysaccharides as the main structural components, is therefore crucial for the understanding of its function. We have here applied microrheology, based on optically trapped micrometre-sized colloids, to the PCM of cultured PC3 prostate cancer cells. This technology allowed us to measure the extremely soft response of the PCM, with approximately 1 µm height resolution. Exogenously added aggrecan, a hyaluronan-binding proteoglycan, caused a remarkable increase in thickness of the viscoelastic layer and also triggered filopodia-like protrusions. The viscoelastic response of the PCM, however, did not change significantly.

8. 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.
9. 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.
10. R. G. Bacabac, D. Mizuno, A. Vatsa, C.F. Schmidt, F.C. MacKintosh, J. Van Loon, J. Klein-Nulend, and T. Smit , "Round versus flat : bone cell norphology, elasticity, and mechanosensing" Journal of biomechanics 41, (7), pp.1590-pp.1598b (2008)
, Journal of biomechanics , 2008.08.
11. 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.
12. Mizuno, D (Mizuno, D); Hattori, K (Hattori, K); Sakai, K (Sakai, K); Takagi, K (Takagi, K), Dynamic measurement of surface properties with Ripplon spectroscopy, 1998 IEEE ULTRASONICS SYMPOSIUM - PROCEEDINGS, VOLS 1 AND 2, 1121-1124.
1. Daisuke Mizuno, Levy statistics and dynamics in active cytoskeletons, 2013 SPP Physics Congress, 2013.10.
2. Daisuke Mizuno, Levy statistics and dynamics in active cytoskeletons, Taiwan International Workshop on Biological Physics and Complex Systems (BioComplex-Taiwan-2013), 2013.07.
3. 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.
Membership in Academic Society
  • biophysical socioety
  • 2006 Bacabac, R.G., Mizuno, D., Vatsa, A., Schmidt, C., MacKintosh, F.,Van Loon, J.J.W.A., Klein-Nulend, J., Smit, T.H.(Amsterdam, The Netherlands) “Round versus flat: Bone cell morphology, elasticity and mechanosensing”
  • "Nonequilibrium mechanics of active cytoskeletal networks", D. Mizuno, C. Tardin, C.F. Schmidt, F.C. MacKintosh, Science, 315, 370-373 (2007)
    "High resolution probing of cellular force transmission", D. Mizuno, R.G. Bacabac, C. Tardin, D. Head, C.F. Scmidt, Phys. Rev. Lett.. 102, 168102 (2009)

  • In much the same way that each of our bodies depends on bones for mechanical integrity and strength, each cell within our bodies is mechanically supported by a skeleton of stiff proteins, called the cytoskeleton. Furthermore, analogous to how our bones are held and moved by muscles, the cytoskeleton is activated by molecular motors, which are nanometer-sized force-generating enzymes. The interior of cells is driven far from equilibrium by such force-generating machinery. In order to study the physics governing such biological systems, developing a new technology to quantify the nonequilibrium property is essential. In this study, mechanical activity similar to that of living cells were investigated in a simplified model system composed of a cytoskeletal protein (actin) with a crosslinker and a motor (myosin).

    In order to investigate the non-equilibrium behavior of the model system, Daisuke Mizuno had developed a novel laser-based technique for simultaneous active and passive microrheology. With this technique, the degree of nonequilibrium activity in the model system was quantified by the violation of the fluctuation-dissipation theorem. The viscoelasticity and internal stresses of such an active material were simultaneously quantified for the first time. It is found that the model cytoskeleton exhibits local contractions similar to living cells, and that these contractions stiffen the system up to 100 times in a manner that can be controlled. A quantitative nonequilibrium physical model to explain those behaviors was also presented.
    These findings demonstrate that a remarkably simple system, with just three components, can reproduce key phenomena also observed in far more complex living cells. The artificial cytoskeleton designed in this study is an adaptive/active system that can tune its own mechanical properties, as with cells or tissues. This provides new fundamental insights for biological science and design principles for materials science.