Patterning in stratified epithelia depends on cell-cell adhesion.

Epithelia consist of proliferating and differentiating cells that often display patterned arrangements. However, the mechanism regulating these spatial arrangements remains unclear. Here, we show that cell-cell adhesion dictates multicellular patterning in stratified epithelia. When cultured keratinocytes, a type of epithelial cell in the skin, are subjected to starvation, they spontaneously develop a pattern characterized by areas of high and low cell density. Pharmacological and knockout experiments show that adherens junctions are essential for patterning, whereas the mathematical model that only considers local cell-cell adhesion as a source of attractive interactions can form regions with high/low cell density. This phenomenon, called cell-cell adhesion-induced patterning (CAIP), influences cell differentiation and proliferation through Yes-associated protein modulation. Starvation, which induces CAIP, enhances the stratification of the epithelia. These findings highlight the intrinsic self-organizing property of epithelial cells.

Two-dimensional hydrodynamic simulation for synchronized oscillatory flows in two collapsible channels connected in parallel.

We investigated self-sustained oscillation in a collapsible channel, in which a part of one rigid wall is replaced by a thin elastic wall, and synchronization phenomena in the two channels connected in parallel. We performed a two-dimensional hydrodynamic simulation in a pair of collapsible channels which merged into a single channel downstream. The stable synchronization modes depended on the distance between the deformable region and the merging point; only an in-phase mode was stable for the large distance, in-phase and antiphase modes were bistable for the middle distance, and again only an in-phase mode was stable for the small distance. An antiphase mode became stable through the subcritical pitchfork bifurcation by decreasing the distance. Further decreasing the distance, the antiphase mode became unstable through the subcritical Neimark-Sacker bifurcation. We also clarified the distance dependences of the amplitude and frequency for each stable synchronization mode.

Activity-induced diffusion recovery in crowded colloidal suspensions.

We show that the forces generated by active enzyme molecules are strong enough to influence the dynamics of their surroundings under artificial crowded environments. We measured the behavior of polymer microparticles in a quasi-two-dimensional system under aqueous environment, at various area fraction values of particles. In the presence of enzymatic activity, not only was the diffusion of the suspended particles enhanced at shorter time-scales, but the system also showed a transition from subdiffusive to diffusive dynamics at longer time-scale limits. Similar observations were also recorded with enzyme-functionalized microparticles. Brownian dynamics simulations have been performed to support the experimental observations.

Periodical alternation between precipitation and dissolution of camphor solid film on an ethanol solution.

Rhythmic behaviors are generally observed in nonlinear chemical reactions such as the Belousov-Zhabotinsky reaction and enzymatic reactions. Similarly, a simple phase change can also lead to rhythmic behavior. It has been reported previously that camphor solid films alternate between generation and disappearance on ethanol (EtOH) solution, and a phenomenological mechanism has been suggested for this. The evaporation of EtOH decreases the temperature on the surface of the solution via vaporization heat and induces precipitation in the camphor solid film. At this time, the film prevents evaporation, and thus, the surface temperature increases due to thermal diffusion from the atmosphere, resulting in dissolution of the solid film. To verify the previously suggested phenomenological mechanism, we controlled the evaporation rate of EtOH using a porous plastic cover. As a result, the period of oscillation increased with decreasing pore diameter, and finally, the oscillation did not occur without pore in the cover, where the camphor solid film was not observed. Additionally, a new mathematical model was proposed, and the numerical calculations agreed well with experimental observations. Linear stability and bifurcation analyses revealed the detailed mechanism of this phenomenon, which agreed well with the phenomenological explanation mentioned above.

Shear-Induced Nonequilibrium Patterns in Lipid Bilayer Membranes Exhibiting Phase Separation.

The nonequilibrium dynamics of a fluid lipid membrane under external stimuli is an important issue that spans disciplines such as soft matter, biophysical chemistry, and interface science. This study investigated the dynamic response of lipid vesicles with order-disorder phase separation, which mimics a plasma membrane heterogeneity, to shear flow. Lipid vesicles were immobilized in a microfluidic chamber, and shear-induced nonequilibrium patterns on the membrane surface were observed by an optical microscope. We found that phase-separated membranes exhibit a dissipative structure of stripe patterns along the vortex flow on the membrane surface, and the number of stripes increased with the flow rate. At a high flow rate, the membrane exhibited a stripe-to-wave transition, where striped domains often migrated and the replacement of two different phases happened at vortex centers with time. We obtained a dynamic phase diagram of the shear-induced wave pattern by changing the flow rate, membrane components, and temperature. These findings could provide insight into the dissipative structures of lipid membranes out of equilibrium and flow-mediated mechanotransduction of biological membranes.

Erratum: Pairing-induced motion of source and inert particles driven by surface tension [Phys. Rev. E 106, 024604 (2022)].

This corrects the article DOI: 10.1103/PhysRevE.106.024604.

Phospholipid Molecular Layer that Enhances Distinction of Odors Based on Artificial Sniffing.

We propose a novel odor-sensing system based on the dynamic response of phospholipid molecular layers for artificial olfaction. Organisms obtain information about their surroundings based on multidimensional information obtained from sniffing, i.e., periodic perturbations. Semiconductor- and receptor-based odor sensors have been developed previously. However, these sensors predominantly identify odors based on one-dimensional information, which limits the type of odor molecule they can identify. Therefore, the development of odor sensors that mimic the olfactory systems of living organisms is useful to overcome this limitation. In this study, we developed a novel odor-sensing system based on the dynamics of phospholipids that responds delicately to chemical substances at room temperature using multidimensional information obtained from periodic perturbations. Odor molecules are periodically supplied to the phospholipid molecular layer as an input sample. The waveform of the surface tension of the phospholipid molecular layer changes depending on the odor molecules and serves as an output. Such characteristic responses originating from the dynamics of odor molecules on the phospholipid molecular layer can be reproduced numerically. The phospholipid molecular layer amplified the information originating from the odor molecule, and the mechanism was evaluated by using surface pressure-area isotherms. This paper offers a platform for an interface-chemistry-based artificial sniffing system as an active sensor and a novel olfactory mechanism via physicochemical responses of the receptor-independent membranes of the organism.

On the reaction-diffusion type modelling of the self-propelled object motion.

In this study, we propose a mathematical model of self-propelled objects based on the Allen-Cahn type phase-field equation. We combine it with the equation for the concentration of surfactant used in previous studies to construct a model that can handle self-propelled object motion with shape change. A distinctive feature of our mathematical model is that it can represent both deformable self-propelled objects, such as droplets, and solid objects, such as camphor disks, by controlling a single parameter. Furthermore, we demonstrate that, by taking the singular limit, this phase-field based model can be reduced to a free boundary model, which is equivalent to the [Formula: see text]-gradient flow model of self-propelled objects derived by the variational principle from the interfacial energy, which gives a physical interpretation to the phase-field model.

Mathematical modeling for the synchronization of two interacting active rotors.

We investigate the synchronization of active rotors. A rotor is composed of a free-rotating arm with a particle that releases a surface-active chemical compound. It exhibits self-rotation due to the surface tension gradient originating from the concentration field of the surface-active compound released from the rotor. In a system with two active rotors, they should interact through the concentration field. Thus, the interaction between them does not depend only on the instantaneous positions, but also on the dynamics of the concentration field. By numerical simulations, we show that in-phase and antiphase synchronizations occur depending on the distance between the two rotors. The stability of the synchronization mode is analyzed based on phase reduction theorem through the calculation of the concentration field in the co-rotating frame with the active rotor. We also confirm that the numerical results meet the prediction by theoretical analyses.

Two-dimensional hydrodynamic simulation for synchronization in coupled density oscillators.

A density oscillator is a fluid system in which oscillatory flow occurs between different density fluids through the pore connecting them. We investigate the synchronization in coupled density oscillators using two-dimensional hydrodynamic simulation and analyze the stability of the synchronous state based on the phase reduction theory. Our results show that the antiphase, three-phase, and 2-2 partial-in-phase synchronization modes spontaneously appear as stable states in two, three, and four coupled oscillators, respectively. The phase dynamics of coupled density oscillators is interpreted with their sufficiently large first Fourier components of the phase coupling function.

Zonula occludens-1 distribution and barrier functions are affected by epithelial proliferation and turnover rates.

Zonula occludens-1 (ZO-1) is a scaffolding protein of tight junctions, which seal adjacent epithelial cells, that is also expressed in adherens junctions. The distribution pattern of ZO-1 differs among stratified squamous epithelia, including that between skin and oral buccal mucosa. However, the causes for this difference, and the mechanisms underlying ZO-1 spatial regulation, have yet to be elucidated. In this study, we showed that epithelial turnover and proliferation are associated with ZO-1 distribution in squamous epithelia. We tried to verify the regulation of ZO-1 by comparing normal skin and psoriasis, known as inflammatory skin disease with rapid turnover. We as well compared buccal mucosa and oral lichen planus, known as an inflammatory oral disease with a longer turnover interval. The imiquimod (IMQ) mouse model, often used as a psoriasis model, can promote cell proliferation. On the contrary, we peritoneally injected mice mitomycin C, which reduces cell proliferation. We examined whether IMQ and mitomycin C cause changes in the distribution and appearance of ZO-1. Human samples and mouse pharmacological models revealed that slower epithelial turnover/proliferation led to the confinement of ZO-1 to the uppermost part of squamous epithelia. In contrast, ZO-1 was widely distributed under conditions of faster cell turnover/proliferation. Cell culture experiments and mathematical modelling corroborated these ZO-1 distribution patterns. These findings demonstrate that ZO-1 distribution is affected by epithelial cell dynamics.

New types of complex motion of a simple camphor boat.

We discuss the motion of a rectangular camphor boat, considering the position of a camphor pill in relation to the boat's stern as the control parameter. The boat moves because the pill releases surface active molecules that decrease the surface tension and support the motion. We introduce a new experimental system in which the boat rotates on a long arm around the axis located at the centre of a Petri dish; thus, the motion is restricted to a circle and can be studied under stationary conditions for a long time. The experiments confirmed two previously reported modes of motion: continuous motion when the pill was located at the boat edge and pulsating (intermittent) motion if it was close to the boat centre (Suematsu et al., J. Phys. Chem. C, 2010, 114(21), 9876-9882). For intermediate pill locations, we observed a new, unreported type of motion characterised by oscillating speed (i.e. oscillating motion). Different modes of motion can be observed for the same pill location. The experimental results are qualitatively confirmed using a simple reaction-diffusion model of the boat evolution used in the above-mentioned paper.

Appearance and suppression of Turing patterns under a periodically forced feed.

Turing instability is a general and straightforward mechanism of pattern formation in reaction-diffusion systems, and its relevance has been demonstrated in different biological phenomena. Still, there are many open questions, especially on the robustness of the Turing mechanism. Robust patterns must survive some variation in the environmental conditions. Experiments on pattern formation using chemical systems have shown many reaction-diffusion patterns and serve as relatively simple test tools to study general aspects of these phenomena. Here, we present a study of sinusoidal variation of the input feed concentrations on chemical Turing patterns. Our experimental, numerical and theoretical analysis demonstrates that patterns may appear even at significant amplitude variation of the input feed concentrations. Furthermore, using time-dependent feeding opens a way to control pattern formation. The patterns settled at constant feed may disappear, or new patterns may appear from a homogeneous steady state due to the periodic forcing.

Domain dynamics of phase-separated lipid membranes under shear flow.

The dynamical behaviour of lateral domains on phase-separated lipid vesicles under external flow is reported. A microfluidic chamber was used for the immobilization of vesicles and the application of shear. Microscopic observation revealed that domains tended to be localized at the vortex center and to exhibit a stripe morphology as the flow speed increased. We clarified the dependency of domain behaviors on the flow speed and lipid mixing fraction. The cholesterol ratio in the membrane affected these domain behaviors. Next, we investigated the growth of domains under flow. We discuss the mechanism of these trends by considering the free energy of phase separation, and reproduce the experimental results by numerical simulations. These findings may lead to a better understanding of the dynamical properties of the membrane under nonequilibrium situations and the biophysical mechanism of cellular mechanotransduction.

Anomalous diffusion and transport by a reciprocal convective flow.

Under low-Reynolds-number conditions, dynamics of convection and diffusion are usually considered separately because their dominant spatial and temporal scales are different, but cooperative effects of convection and diffusion can cause diffusion enhancement [Koyano et al., Phys. Rev. E 102, 033109 (2020)2470-004510.1103/PhysRevE.102.033109]. In this paper, such cooperative effects are investigated in detail. Numerical simulations based on the convection-diffusion equation revealed that anisotropic diffusion and net shift as well as diffusion enhancement occur under a reciprocal flow. Such anomalous diffusion and transport are theoretically derived by the analyses of the Langevin dynamics.

Pairing-induced motion of source and inert particles driven by surface tension.

We experimentally and theoretically investigate systems with a pair of source and inert particles that interact through a concentration field. The experimental system comprises a camphor disk as the source particle and a metal washer as the inert particle. Both are floated on an aqueous solution of glycerol at various concentrations, where the glycerol modifies the viscosity of the aqueous phase. The particles form a pair owing to the attractive lateral capillary force. As the camphor disk spreads surface-active molecules at the aqueous surface, the camphor disk and metal washer move together, driven by the surface tension gradient. The washer is situated in the front of the camphor disk, keeping the distance constant during their motion, which we call a pairing-induced motion. The pairing-induced motion exhibited a transition between circular and straight motions as the glycerol concentration in the aqueous phase changed. Numerical calculations using a model that considers forces caused by the surface tension gradient and lateral capillary interaction reproduced the observed transition in the pairing-induced motion. Moreover, this transition agrees with the result of the linear stability analysis on the reduced dynamical system obtained by the expansion with respect to the particle velocity. Our results reveal that the effect of the particle velocity cannot be overlooked to describe the interaction through the concentration field.

Complexity and bifurcations in the motion of a self-propelled rectangle confined in a circular water chamber.

We consider the motion of a self-propelled object of rectangular shape inside a circular water chamber. The mathematical model of self-motion includes equations for the orientation and location of the rectangle and reaction-diffusion equation with an effective diffusion coefficient for the time evolution of the surface concentration of active molecules. Numerical simulations of motion were performed for different values of the ratio between the supply rate S and the evaporation rate a of active molecules. Treating S0 = S/a as a control parameter, we found the critical behavior in variables characterizing the trajectory and identified different types of motion. If the value of S0 is small, the rectangle rests at the chamber center. For larger S0, a reciprocal motion during which the rectangle passes through the center is observed. At yet higher supply rates, the star-polygonal motion appears, and the trajectory remains at a distance from the chamber center. In the experiments with a rectangle made of camphor-camphene-polypropylene plastic moving in a Petri dish, we observed the transition from the star-polygonal motion to the reciprocal motion in time. This transition can be understood on the basis of the developed model if we assume that the supply rate decreases in time.

Bifurcation structure of the flame oscillation.

A flame exhibits a limit-cycle oscillation, which is called "flame flickering" or "puffing," in a certain condition. We investigated the bifurcation structure of the flame oscillation in both simulation and experiment. We performed a two-dimensional hydrodynamic simulation by employing the flame sheet model. We reproduced the flame oscillation and investigated the parameter dependencies of the amplitude and frequency on the fuel-inlet diameter. We also constructed an experimental system, in which we could finely vary the fuel-inlet diameter, and we investigated the diameter-dependencies of the amplitude and frequency. In our simulation, we observed the hysteresis and bistability of the stationary and oscillatory states. In our experiments, we observed the switching between the stationary and oscillatory states. As fluctuations can induce the switching in the bistable system, switching observed in our experiments suggested the bistability of the two states. Therefore, we concluded that the oscillatory state appeared from the stationary state through the subcritical Andronov-Hopf bifurcation in both the simulation and experiment. The amplitude was increased and the frequency was decreased as the fuel-inlet diameter was increased. In addition, we visualized the vortex structure in our simulation and discussed the effect of the vortex on the flame dynamics.

Collagen XVII deficiency alters epidermal patterning.

Vertebrates exhibit patterned epidermis, exemplified by scales/interscales in mice tails and grooves/ridges on the human skin surface (microtopography). Although the role of spatiotemporal regulation of stem cells (SCs) has been implicated in this process, the mechanism underlying the development of such epidermal patterns is poorly understood. Here, we show that collagen XVII (COL17), a niche for epidermal SCs, helps stabilize epidermal patterns. Gene knockout and rescue experiments revealed that COL17 maintains the width of the murine tail scale epidermis independently of epidermal cell polarity. Skin regeneration after wounding was associated with slender scale epidermis, which was alleviated by overexpression of human COL17. COL17-negative skin in human junctional epidermolysis bullosa showed a distinct epidermal pattern from COL17-positive skin that resulted from revertant mosaicism. These results demonstrate that COL17 contributes to defining mouse tail scale shapes and human skin microtopography. Our study sheds light on the role of the SC niche in tissue pattern formation.