No Arabic abstract
Liquid-liquid phase separation occurs not only in bulk liquid, but also on surfaces. In physiology, the nature and function of condensates on cellular structures remain unexplored. Here, we study how the condensed protein TPX2 behaves on microtubules to initiate branching microtubule nucleation, which is critical for spindle assembly in eukaryotic cells. Using fluorescence, electron, and atomic force microscopies and hydrodynamic theory, we show that TPX2 on a microtubule reorganizes according to the Rayleigh-Plateau instability, like dew droplets patterning a spider web. After uniformly coating microtubules, TPX2 forms regularly spaced droplets from which branches nucleate. Droplet spacing increases with greater TPX2 concentration. A stochastic model shows that droplets make branching nucleation more efficient by confining the space along the microtubule where multiple necessary factors colocalize to nucleate a branch.
Interfaces between stratified epithelia and their supporting stromas commonly exhibit irregular shapes. Undulations are particularly pronounced in dysplastic tissues and typically evolve into long, finger-like protrusions in carcinomas. In a previous work (Basan et al., Phys. Rev. Lett. 106, 158101 (2011)), we demonstrated that an instability arising from viscous shear stresses caused by the constant flow due to cell turnover in the epithelium could drive this phenomenon. While interfacial tension between the two tissues as well as mechanical resistance of the stroma tend to maintain a flat interface, an instability occurs for sufficiently large viscosity, cell-division rate and thickness of the dividing region in the epithelium. Here, extensions of this work are presented, where cell division in the epithelium is coupled to the local concentration of nutrients or growth factors diffusing from the stroma. This enhances the instability by a mechanism similar to that of the Mullins-Sekerka instability in single-diffusion processes of crystal growth. We furthermore present the instability for the generalized case of a viscoelastic stroma.
Cellular appendages conferring motility, such as flagella or cilia, are known to synchronise their periodic beats. The origin of synchronisation is a combination of long-range hydrodynamic interactions with physical mechanisms allowing the phases of these biological oscillators to evolve. Two of such mechanisms have been identified by previous work, the elastic compliance of the periodic orbit or oscillations driven by phase-dependent biological forcing. To help uncover the physical mechanism for hydrodynamic synchronisation most essential overall in biology, we theoretically investigate the effect of strong confinement on the effectiveness of hydrodynamic synchronisation. We use minimal models where appendages are modelled as rigid spheres forced to move along circular trajectories near a rigid surface. Strong confinement is modelled by adding a second nearby surface, parallel to the first one, where the distance between the surfaces is much smaller than the typical distance between the cilia. We calculate separately the impact of confinement on the synchronisation dynamics of the elastic compliance and the force modulation mechanisms and compare our results to the case with no confinement. Applying our results to the biologically-relevant situation of nodal cilia, we show that force modulation is a mechanism that leads to phase-locked states under strong confinement that are very similar to those without confinement as a difference with the elastic compliance mechanism. Our results point therefore to the robustness of force modulation for synchronisation, an important feature for biological dynamics that suggests it could be the most essential physical mechanism overall in arrays of nodal cilia. We further examine the distinct situation of primary cilia and show in that case that the difference in robustness of the mechanisms is not as pronounced but still favours the force modulation.
Combining high-resolution single cell tracking experiments with numerical simulations, we show that starvation-induced fruiting body (FB) formation in Myxococcus xanthus is a phase separation driven by cells that tune their motility over time. The phase separation can be understood in terms of cell density and a dimensionless Peclet number that captures cell motility through speed and reversal frequency. Our work suggests that M. xanthus take advantage of a self-driven non-equilibrium phase transition that can be controlled at the single cell level.
Compared to agile legged animals, wheeled and tracked vehicles often suffer large performance loss on granular surfaces like sand and gravel. Understanding the mechanics of legged locomotion on granular media can aid the development of legged robots with improved mobility on granular surfaces; however, no general force model yet exists for granular media to predict ground reaction forces during complex limb intrusions. Inspired by a recent study of sand-swimming, we develop a resistive force model in the vertical plane for legged locomotion on granular media. We divide an intruder of complex morphology and kinematics, e.g., a bio-inspired robot L-leg rotated through uniform granular media (loosely packed ~ 1 mm diameter poppy seeds), into small segments, and measure stresses as a function of depth, orientation, and direction of motion using a model leg segment. Summation of segmental forces over the intruder predicts the net forces on both an L-leg and a reversed L-leg rotated through granular media with better accuracy than using simple one-dimensional penetration and drag force models. A multi-body dynamic simulation using the resistive force model predicts the speeds of a small legged robot (15 cm, 150 g) moving on granular media using both L-legs and reversed L-legs.
We consider the dynamics of a rigid filament in a motor protein assay under external loading. The motor proteins are modeled as active harmonic linkers with tail ends immobilized on a substrate. Their heads attach to the filament stochastically to extend along it, resulting in a force on the filament, before detaching. The rate of extension and detachment are load dependent. Here we formulate and characterize the governing dynamics in the mean field approximation using linear stability analysis, and direct numerical simulations of the motor proteins and filament. Under constant loading, the system shows transition from a stable configuration to instability towards detachment of the filament from motor proteins. Under elastic loading, we find emergence of stable limit cycle oscillations via a supercritical Hopf bifurcation with change in activity and the number of motor proteins. Numerical simulations of the system for large number of motor proteins show good agreement with the mean field predictions.