東京大学 竹内研究室 公式ウェブページ

細菌の細胞質内はタンパク質やRNAなどの高分子によって非常に混み合ってお り、その空間を細胞膜と細胞壁が閉じ込めています。細胞質内の乾燥マス密度 （以下、マス密度）は300 mg/mLにのぼり、この高密度環境が細胞内における 酵素反応などの生体内反応の効率に重要だと考えられています。このように細 胞のマス密度は細胞生理に重要な要素であるにも関わらず、live single-cell での測定が非常に困難であることから、その制御機構についてはほとんど明ら かになっていません。そこで、私たちは枯草菌の細胞をモデルとし、定量位相 顕微鏡の一種であるSpatial light interference microscopy（SLIM）を用い て、live single-cellのマス密度変化を定量しました。その結果、これまでに 予想されていた通り、多くの生育条件において細胞のマス密度は一定に維持さ れていましたが、細胞形態を変化させた場合に限って、細胞のマス密度は非常 にダイナミックに変化していることが分かりました。このことから、体積や表 面積などの細胞形態に関わる変数がマス密度と関係があると考え、現在はその 定式化に取り組んでいます。当日は、これらの定量結果に加え、生物学的な分 子機構にも触れながら、議論させていただきたいと思います。

Stochastic thermodynamics describes the evolution of a system in contact with a thermostat, when fluctuations dominate. This is implicitly assumed to occur most often for micron-scale systems.

We develop experiments at human-scale, i.e. from millimeters to dozen of centimeters. For instance one is based on the principle of Brownian motion, however with a granular gas as heat bath [1]. A core feature is the intrinsic dissipation of this thermostat, that needs to be compensated by a power supply. This bath, in such a Non-Equilibrium Steady State (NESS), seems definitely distinct from a drop of water !

However, our main outcome is that, for all criteria investigated, no qualitative departure could be evidenced by changing the scale or the dissipation : a heuristic use of the Gallavotti-Cohen Fluctuation Theorem and of the Fluctuation-Dissipation Theorem give an ‘effective temperatures’ kT_eff. consistent to within 10% [2] ; the heat flux between two such NESS baths follows the Fourier law on the average [3] ; and the fluctuations of heat flux follows the extended fluctuation theorem (XFT) proposed by Jarzynski et al. in 2004 [4,5].
We explain how kT_eff., defined and mesured in a NESS, exhibits typical value around 10^-6 J, considerably larger than those of molecular systems (kBT~10^-21 J). It however behaves as a unual equilibrium temperature !

At this point, we considered the analogy is validated, as far as stochastic thermodynamics concepts are concerned, and turned to further investigations. We checked that this approach holds in other kinds of NESS baths, such as an elastic plate in wave turbulence regime [6], or large Reynolds number turbulent flow.

We will discuss some woork in progress, and draw some perspectives for this convenient experimental benchtest, in the direction of the relations between energy and information, for instance, but not only.

Références :
[1] Naert A., EuroPhys. Lett. 97 2 (2012) 20010,
[2] J.-Y. Chastaing, J.-C. Géminard and A. Naert,
J. Stat. Mech. 073212 (2017)
[3] Lecomte C.-E. and Naert A., J. Stat. Mech., P11004 (2014),
[4] C. Jarzynski and D. K. Wójcik, Phys. Rev. Lett., vol. 92, p. 230602, Jun 2004.
[5] M. Lamèche, A. Naert, to be published
[6] B. Apffel, A. Naert, S. Aumaître, J. Stat. Mech., vol. 2019, p. 013209, jan 2019

Knits mechanical properties are fundamentally different from those of its constitutive yarn. For instance, a fabric knitted with an inextensible yarn demonstrates a surprising inclination for deformability. Like mechanical systems where geometry plays a preponderant role, such as origami, the mechanical response of knitted fabrics is governed by the pattern imposed on the yarn. In the process of knitting, the yarn is constrained to bend and to cross itself following a periodic pattern, anchoring its topology. The three factors which determine the mechanical response of a knit are the elasticity of the yarn, its topology, and friction between crossing strands. We explored several phenomena that arise from the interplay of these factors, such as the elasticity of a stretched fabric or the fluctuations in the mechanical response revealing an avalanching dynamics.

Close to the onset of an instability, it is expected that fluctuations can play a role. In general, fluctuations act additively (broadly speaking, their effect do not depend on the amplitude of the unstable field) and are responsible for a variety of effects such as the well known anomalous critical exponents of equilibrium phase transition.

In out of equilibrium systems, fluctuations can be multiplicative: their effect vanish when the amplitude of the unstable mode is zero. Several new effects appear. During this seminar I will discuss in particular two topics: what happen to the onset (is it still defined, how to calculate
it)? and what happen above onset (focussing on the so-called on-off intermittent regime).

The presented results will be illustrated with examples in the context of instabilities in fluid dynamics and magneto hydrodynamics.

Already more than 4 decades ago the possibility of ferromagnetic nematic liquid crystals has been postulated [1] by combining ferromagnetic nanoparticles with a nematic solvent. First experiments along these ideas were carried out immediately [2], giving rise to ferronematics with no spontaneous magnetization. Only a few years ago [3], with the development of suitably well-characterized magnetic nanoparticles, truly ferromagnetic nematics could be synthesized and analyzed thus establishing the first room temperature multiferroic liquid system. The static properties including magneto-optic and converse magnetoelectric effects were demonstrated [4]. Quite recently the study of the dynamics of truly ferromagnetic nematic liquid crystals properties has started [5]. It was demonstrated in [5] that a dissipative cross-coupling between the two order parameters [6], magnetization and director, is essential to account for the dynamic experimental results quantitatively. Recent developments [7,8] in the dynamic domain include investigations of the light scattering behavior as well as the coupling to flow including shear flows and the analog of the Miesowicz viscosities familiar from usual nematic liquid crystals.

[1] F. Brochard and P.G. de Gennes, J. Phys. 31, 691 (1970).
[2] J. Rault, P.E. Cladis, and J.-P. Burger, Phys. Lett. A 32, 199 (1970).
[3] A. Mertelj, D. Lisjak, M. Drofenik, and M. Copic, Nature 504, 237 (2013).
[4] A. Mertelj, N. Osterman, D. Lisjak, and M. Copic, Soft Matter 10, 9065 (2014).
[5] T. Potisk et al., Phys. Rev. Lett. 119, 097802 (2017).
[6] E. Jarkova, H. Pleiner, H.-W. Mueller and H.R. Brand, J. Chem. Phys. 118, 2422 (2003).
[7] T. Potisk et al., Phys. Rev. E 97, 012701 (2018).
[8] T. Potisk et al., to be published.

たった一つの生命現象を発現させるためにも、細胞中では無数の分子が働いている。しかも、これらの分子は単独ではなく、分子ネットワークを作り機能している。このような複雑系の実体を知るには、その現場を正確に画像化することが肝要である。このような目標に対して、生体試料のための電子顕微鏡は、他の方法と比べて目覚ましく発展しており、このような複雑系の一部が見え始めている。例えば、細胞外であれば、結晶化せずに生体分子複合体の原子モデルが手に入るようになっている。また、分解能に弱点があった光学顕微鏡も、急速に分解能の改善が見られ、これまで見えなかった微細な細胞内構造が観測されてきている。このような状況の中、我々は急速凍結することで固定化した試料を観察する蛍光顕微鏡（クライオ蛍光顕微鏡）を独自開発することで、その解像度を分子レベルに引き上げることに成功した[1-3]。講演では、生体試料イメージングの現状を簡単に紹介した後に、我々の研究について紹介したい。

[1] S. Fujiyoshi et al.; Phys. Rev. Lett. 100, 168101 (2008).
[2] S. Fujiyoshi et al.; Phys. Rev. Lett. 106, 078101 (2011).
[3] T. Furubayashi et al.; J. Am. Chem. Soc. 139, 8990 (2017).

Active colloids and liquid crystals are capable of locally converting the macroscopically-supplied energy into directional motion and promise a host of new applications, ranging from drug delivery to cargo transport at the mesoscale. In this presentation, I will discuss how knotted fields and defects in liquid crystals can locally transform electric energy to translational motion and allow for the transport of cargo along directions dependent on frequency of the applied electric field. By combining polarized optical video microscopy and numerical modeling that reproduces both the equilibrium structures of solitons and their temporal evolution in applied fields, we uncover the physical underpinnings behind this reconfigurable motion and study how it depends on the structure and topology of defects. In my lecture I will show that, unexpectedly, the directional motion of the studied defects with and without the cargo arises mainly from the asymmetry in rotational dynamics of molecular ordering in liquid crystal, rather than from the asymmetry of fluid flows, as in conventional active soft matter systems.

I will present recent experimental results on dense bacterial suspensions obtained in the groups of Masaki Sano (University of Tokyo), Yilin Wu (Chinese University of Hong Kong), and Hepeng Zhang (Shanghai Jiaotong University). I will put them in context, situating them within our current knowledge of active matter, stressing differences and similarities. Particular attention will be paid to the modeling efforts already deployed or to be developed in order to understand the fascinating large-scale phenomena observed by these 3 groups.

Kinetic roughening is the process by which interfaces develop a self-affine roughness in non-equilibrium systems. The interfaces can represent domain walls, the surface of a growing crystal, the edge of a bacterial colony, etc. We present two consequences of non-equilibrium kinetic roughening in two dimensions.

Our first story reports on the non-equilibrium diffusion of two-dimensional cluster. These clusters can represent e.g. an Ising droplet driven by a field, a monolayer island growing on a facet during crystal growth or dissolution, or an expanding bacterial colony. We find that the mean square displacement of the center of mass of clusters exhibit a transition from superdiffusive to subdiffusive diffusion during growth, with exponents controlled by the kinetic roughening of the cluster edge.

The second story focuses of the collision between growth fronts. We here aim to model e.g. the process by which grain boundaries form in graphene, or by which different expanding bacterial films collide. We claim that this process can be seen as non-trivial generalization of first passage processes. We show that the spatio-temporal roughness of the collision is controlled by the roughness accumulated before the collision. The distribution of times of collision, and the roughness of interface after collision are shown to obey dynamic scaling, and combine linearly the distributions of the two fronts before collision.

REFERENCES
1. Non-equilibrium cluster diffusion during growth and evaporation in two dimensions (editor's suggestion), Y. Saito, M. Dufay, O. Pierre-Louis, Phys Rev. Lett. 108, 245504 (2012)
2. Non-equilibrium interface collisions, F.A. Reis, O. Pierre-Louis, preprint (2016)

Adult tissues undergo rapid turnover as mature cells are continuously lost, and new cells arise through cell division. The balance between gain and loss of cells must be finely orchestrated to maintain tissues, but how this balance is achieved remains largely unknown. For the skin, it had been assumed that the fate choices of stem cells (division or differentiation) are made strictly cell-autonomously. Here we recorded every stem cell fate choice within mouse skin epidermal regions over one week and found that, far from being cell-autonomous, stem cell loss by differentiation was compensated by direct neighboring division[1]. Furthermore, division events were triggered by neighbor differentiation and not vice versa, showing differentiation-dependent division as the core feature of homeostatic control.

In this presentation, we will formalize the problem of tissue homeostasis using a macroscopic nonequilibrium model setup[2]. Starting from an interacting particle system with Brownian motion, we show how the coarse-graining of our model will lead to the effective dynamics of the Voter model (DP2). We will then explain the pitfall in two-dimensions of using scaling relations of the type used before for the clonal fate trace of cells, and illustrate the workaround used in the new data analysis to definitively show the existence of cell-to-cell fate correlation.

[1] Mesa, Kawaguchi et al., Biorxiv (2017) doi: https://doi.org/10.1101/155408
[2] Yamaguchi, Kawaguchi, and Sagawa, Phys. Rev. E 96, 012401 (2017)