Active systems can produce a far greater variety of ordered patterns than conventional equilibrium systems. In particular, transitions between disorder and either polar- or nematically ordered phases have been predicted and observed in two-dimensional active systems. However, coexistence between phases of different types of order has not been reported. We demonstrate the emergence of dynamic coexistence of ordered states with fluctuating nematic and polar symmetry in an actomyosin motility assay. Combining experiments with agent-based simulations, we identify sufficiently weak interactions that lack a clear alignment symmetry as a prerequisite for coexistence. Thus, the symmetry of macroscopic order becomes an emergent and dynamic property of the active system. These results provide a pathway by which living systems can express different types of order by using identical building blocks.

Myotube formation by fusion of myoblasts and subsequent elongation of the syncytia is essential for skeletal muscle formation. However, molecules that regulate myotube formation remain elusive. Here we identify PIEZO1, a mechanosensitive Ca2+ channel, as a key regulator of myotube formation. During myotube formation, phosphatidylserine, a phospholipid that resides in the inner leaflet of the plasma membrane, is transiently exposed to cell surface and promotes myoblast fusion. We show that cell surface phosphatidylserine inhibits PIEZO1 and that the inward translocation of phosphatidylserine, which is driven by the phospholipid flippase complex of ATP11A and CDC50A, is required for PIEZO1 activation. PIEZO1-mediated Ca2+ influx promotes RhoA/ROCK-mediated actomyosin assemblies at the lateral cortex of myotubes, thus preventing uncontrolled fusion of myotubes and leading to polarized elongation during myotube formation. These results suggest that cell surface flip-flop of phosphatidylserine acts as a molecular switch for PIEZO1 activation that governs proper morphogenesis during myotube formation.

We have studied the impact of the Al2O3 inter-layer on interface properties of HfO2/InGaAs metal-oxide-semiconductor (MOS) interfaces. We have found that the insertion of the ultrathin Al2O3 inter-layer (2 cycle: 0.2 nm) can effectively improve the HfO2/InGaAs interface properties. The frequency dispersion and the stretch-out of C-V characteristics are improved, and the interface trap density (Dit) value is significantly decreased by the 2 cycle Al2O3 inter-layer. Finally, we have demonstrated the 1-nm-thick capacitance equivalent thickness in the HfO2/Al2O3/InGaAs MOS capacitors with good interface properties and low gate leakage of 2.4 × 10−2 A/cm2.

In the ectopic lymphoid‐like structures present in chronic inflammatory conditions such as rheumatoid arthritis, a subset of human effector memory CD4+ T cells that lacks features of follicular helper T (Tfh) cells produces CXCL13. Here, we report that TGF‐β induces the differentiation of human CXCL13‐producing CD4+ T cells from naïve CD4+ T cells. The TGF‐β‐induced CXCL13‐producing CD4+ T cells do not express CXCR5, B‐cell lymphoma 6 (BCL6), and other Tfh‐cell markers. Furthermore, expression levels of CD25 (IL‐2Rα) in CXCL13‐producing CD4+ T cells are significantly lower than those in FoxP3+ in vitro induced Treg cells. Consistent with this, neutralization of IL‐2 and knockdown of STAT5 clearly upregulate CXCL13 production by CD4+ T cells, while downregulating the expression of FoxP3. Furthermore, overexpression of FoxP3 in naïve CD4+ T cells downregulates CXCL13 production, and knockdown of FoxP3 fails to inhibit the differentiation of CXCL13‐producing CD4+ T cells. As reported in rheumatoid arthritis, proinflammatory cytokines enhance secondary CXCL13 production from reactivated CXCL13‐producing CD4+ T cells. Our findings demonstrate that CXCL13‐producing CD4+ T cells lacking Tfh‐cell features differentiate via TGF‐β signaling but not via FoxP3, and exert their function in IL‐2‐limited but TGF‐β‐rich and proinflammatory cytokine‐rich inflammatory conditions.

Living matter has the extraordinary ability to behave in a concerted manner, which is exemplified throughout nature ranging from the self-organisation of the cytoskeleton to flocks of animals [1–4]. The microscopic dynamics of constituents have been linked to the system’s meso- or macroscopic behaviour in silico via the Boltzmann equation for propelled particles [5–10]. Thereby, simplified binary collision rules between the constituents had to be assumed due to the lack of experimental data. We report here experimentally determined binary collision statistics by studying the recently introduced molecular system, the high density actomyosin motility assay [11–13]. We demonstrate that the alignment effect of the binary collision statistics is too weak to account for the observed ordering transition. The transition density for polar pattern formation decreases quadratically with filament length, which indicates that multi-filament collisions drive the observed ordering phenomenon and that a gas-like picture cannot explain the transition of the system to polar order. The presented findings demonstrate that the unique properties of biological active matter systems require a description that goes well beyond a gas-like picture developed in the framework of kinetic theories.

Constituents of living or synthetic active matter have access to a local energy supply that serves to keep the system out of thermal equilibrium. The statistical properties of such fluctuating active systems differ from those of their equilibrium counterparts. Using the actin filament gliding assay as a model, we studied how nonthermal distributions emerge in active matter. We found that the basic mechanism involves the interplay between local and random injection of energy, acting as an analog of a thermal heat bath, and nonequilibrium energy dissipation processes associated with sudden jump-like changes in the system's dynamic variables. We show here how such a mechanism leads to a nonthermal distribution of filament curvatures with a non-Gaussian shape. The experimental curvature statistics and filament relaxation dynamics are reproduced quantitatively by stochastic computer simulations and a simple kinetic model. active filaments | nonthermal statistics | molecular motors | gliding assay | kinetic model I n active systems, perpetual local energy input prevents relaxation into a thermal equilibrium state (1-3). Examples are living matter (4-10) or appropriately reconstituted or synthetic model systems (11)(12)(13)(14)(15)(16)(17). It is widely accepted that nonthermal fluctuations play a crucial role for the dynamics of active systems (8,9,(18)(19)(20)(21)(22)(23)(24) and may even cause an apparent violation of the fluctuation-dissipation theorem (11). The physical origin of the violation can be attributed to local tensile stresses generated by myosin minifilaments, as shown by rheological measurements of 3D actin networks consisting of myosin II, actin filaments, and cross-linkers (11). Although this study focused on how the macroscopic properties of the active filament network are altered with respect to its equilibrium counterpart, we consider how local stresses generated by motors mesoscopically affect the dynamics and the conformational statistics of individual filaments. To this end, we use the actin gliding assay (25,26), which has become a paradigm of active systems. In this assay, actin filaments are moved by individual nonprocessive myosin motors, which are bound to a substrate. We find that motile filaments in this assay display a nonthermal distribution of curvatures with an exponential shape, which is essentially different from its equilibrium counterpart. Based on our observations, we were able to elucidate the origin of the nonthermal fluctuations in the gliding assay and introduce a mechanism that explains how nonthermal distributions may emerge in active matter systems. The mechanism relies on the interplay between local and random input of energy, acting as an analog of a thermal heat bath, and nonequilibrium energy dissipation processes due to sudden jumplike changes in the system's dynamic variables. We perform stochastic simulations of the filament's dynamics and provide a rationale drawn from kinetic theory. Both approaches quantitatively reproduce the experimental curvature distribution...

Dynamic spatiotemporal patterns that arise from out-of-equilibrium biochemical reactions generate forces in living cells. Despite considerable recent efforts, rational design of spatiotemporal patterns in artificial molecular systems remains at an early stage of development. Here, we describe force generation by a propagating wave of supramolecular nanofibers. Inspired by actin dynamics, a reaction network is designed to control the formation and degradation of nanofibers by two chemically orthogonal stimuli. Real-time fluorescent imaging successfully visualizes the propagating wave based on spatiotemporally coupled generation and collapse of nanofibers. Numerical simulation indicates that the concentration gradient of degradation stimulus and the smaller diffusion coefficient of the nanofiber are critical for wave emergence. Moreover, the force (0.005 pN) generated by chemophoresis and/or depletion force of this propagating wave can move nanobeads along the wave direction.

N/A. Laryngoscope, 2016 127:E67-E74, 2017.