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Tatsuya Fukuyama

Publications and source records attributed to Tatsuya Fukuyama.

5 recordsLinked to original sources

Boundary-shape driven transitions in vortex and oscillatory dynamics of confined epithelial cells

Controlling the collective motion of epithelial cell populations is fundamental for understanding multicellular self-organization and for advancing tissue engineering. Under spatial confinement, cells are known to exhibit either vortex rotation or oscillatory motion depending on boundary geometry, but the mechanisms governing transitions between these states remain unclear. Here, we investigated the collective motion of MDCK cells confined within a doublet circular boundary, where the confinement aspect ratio, defined as the distance between the centers of two circles relative to their radius, can be tuned by varying the degree of overlap. When the overlap is large, cells form a stable vortex. Increasing the confinement aspect ratio destabilizes this vortex and induces oscillatory motion characterized by periodic reversals of migration direction, before ultimately transitioning into disordered dynamics. To elucidate the underlying mechanism, we developed simulations of self-propelled particles incorporating local alignment (LA) and contact inhibition of locomotion (CIL). The model successfully reproduced the experimentally observed transitions from vortices to oscillatory motion and further revealed that an appropriate balance between LA and CIL is critical for stabilizing vortex pairs with velocity reversals. Our findings demonstrate that the confinement aspect ratio serves as a minimal control parameter governing transitions in the collective dynamics of epithelial monolayers.

cond-mat.soft↗

Why epithelial cells collectively move against a traveling signal wave

The response of cell populations to external stimuli plays a central role in biological mechanical processes such as epithelial wound healing and developmental morphogenesis. Wave-like propagation of a signal of ERK MAP kinase has been shown to direct collective migration in one direction; however, the mechanism based on continuum mechanics under a traveling wave is not fully understood. To elucidate how the traveling wave of the ERK kinase signal directs collective migration, we constructed the mechanical model of the epithelial cell monolayer by considering the signal-dependent coordination of contractile stress and cellular orientation. The proposed model was studied by using an optogenetically-controlled cell system where we found that local signal activation induces changes in cell density and orientation with the direction of propagation. The net motion of the cell population occurred relative to the wave, and the migration velocity showed a maximum in resonance with the velocity of the ERK signal wave. The presented mechanical model was further validated in \textit{in vitro} wound healing process.

physics.bio-ph↗

Density-dependent flow generation in active cytoskeletal fluids

The actomyosin cytoskeleton, a protein assembly comprising actin fibers and the myosin molecular motor, drives various cellular dynamics through contractile force generation at high densities. However, the relationship between the density dependence of the actomyosin cytoskeleton and force-controlled ordered structure remains poorly understood. In this study, we measured contraction-driven flow generation by varying the concentration of cell extracts containing the actomyosin cytoskeleton and associated nucleation factors. We observed continuous actin flow toward the center at a critical actomyosin density in cell-sized droplets. Notably, the actin flow demonstrated emergent oscillations, in which tracer advection periodically changed in a stop-and-go fashion in bulk solution. Near the onset of flow, the viscous drag of the actin cytoskeleton decreased the particle transport, after which it rapidly increased. These results indicate that the density-dependent actin flow is generated by a balance between viscous friction and contractile force.

cond-mat.soft↗

Examining the assembly pathways and active microtubule mechanics underlying spindle self-organization

The bipolar organization of the microtubule-based mitotic spindle is essential for the faithful segregation of chromosomes in cell division. Despite our extensive knowledge of genes and proteins, the physical mechanism of how the ensemble of microtubules can assemble into a proper bipolar shape remains elusive. Here, we study the pathways of spindle self-organization using cell-free Xenopus egg extracts and computer-based automated shape analysis. Our microscopy assay allows us to simultaneously record the growth of hundreds of spindles in the bulk cytoplasm and systematically analyze the shape of each structure over the course of self-organization. We find that spindles that are maturing into a bipolar shape take a route that is distinct from those ending up with faulty structures, such as those of a tripolar shape. Moreover, matured structures are highly stable with little occasions of transformation between different shape phenotypes. Visualizing the movement of microtubules further reveals a fraction of microtubules that assemble between extra poles and push the poles apart, suggesting the presence of active extensile force that prevents pole coalescence. Together, we propose that a proper control over the magnitude and location of the extensile, pole-pushing force is crucial for establishing spindle bipolarity while preventing multipolarity.

physics.bio-ph↗

Thermal Molecular Focusing: Tunable Cross Effect of Phoresis and Advection

The control of solute fluxes through either microscopic phoresis or hydrodynamic advection is a fundamental way to transport molecules, which are ubiquitously present in nature and technology. We study the transport of large solute such as DNA driven by a time-dependent thermal field in a polymer solution. Heat propagation of a single heat spot moving back and forth gives rise to the molecular focusing of DNA with frequency-tunable control. We developed a theoretical model, where heat conduction, viscoelastic expansion of walls, and the viscosity gradient of a smaller solute are coupled, and that can explain the underlying hydrodynamic focusing and its interplay with phoretic transports. This cross effect may allow one to design a unique miniaturized pump in microfluidics.

cond-mat.soft↗