Emergence of Spatial Scales and Macroscopic Tissue Dynamics in Active Epithelial Monolayers.

Migrating cells in tissues are often known to exhibit collective swirling movements. In this paper, we develop an active vertex model with polarity dynamics based on contact inhibition of locomotion (CIL). We show that under this dynamics, the cells form steady-state vortices in velocity, polarity, and cell stress with length scales that depend on polarity alignment rate (ζ), self-motility (v0), and cell-cell bond tension (λ). When the ratio λ/v0 becomes larger, the tissue reaches a near jamming state because of the inability of the cells to exchange their neighbors, and the length scale associated with tissue kinematics increases. A deeper examination of this jammed state provides insights into the mechanism of sustained swirl formation under CIL rule that is governed by the feedback between cell polarities and deformations. To gain additional understanding of how active forcing governed by CIL dynamics leads to large-scale tissue dynamics, we systematically coarse-grain cell stress, polarity, and motility and show that the tissue remains polar even on larger length scales. Overall, we explore the origin of swirling patterns during collective cell migration and obtain a connection between cell-level dynamics and large-scale cellular flow patterns observed in epithelial monolayers.

Percolation transition in phase-separating active fluid.

The motility-induced phase separation exhibited by active particles with repulsive interactions is well known. We show that the interaction softness of active particles destabilizes the highly ordered dense phase, leading to the formation of a porous cluster which spans the system. This soft limit can also be achieved if the particle motility is increased beyond a critical value, at which the system clearly exhibits all the characteristics of a standard percolation transition. We also show that in the athermal limit, active particles exhibit similar transitions even at low motility. With these additional new phases, the phase diagram of repulsive active particles is revealed to be richer than what was previously conceived.

A mechano-sensing mechanism for waving in plant roots.

Arabidopsis roots grown on inclined agar surfaces exhibit unusual sinusoidal patterns known as root-waving. The origin of these patterns has been ascribed to both genetic and environmental factors. Here we propose a mechano-sensing model for root-waving, based on a combination of friction induced by gravitropism, the elasticity of the root and the anchoring of the root to the agar by thin hairs, and demonstrate its relevance to previously obtained experimental results. We further test the applicability of this model by performing experiments in which we measure the effect of gradually changing the inclination angles of the agar surfaces on the wavelength and other properties of the growing roots. We find that the observed dynamics is different than the dynamics reported in previous works, but that it can still be explained using the same mechano-sensing considerations. This is supported by the fact that a scaling relation derived from the model describes the observed dependence of the wavelength on the tilt angle for a large range of angles. We also compare the prevalence of waving in different plant species and show that it depends on root thickness as predicted by the model. The results indicate that waving can be explained using mechanics and gravitropism alone and that mechanics may play a greater role in root growth and form than was previously considered.

Role of Delta-Notch signalling molecules on cell-cell adhesion in determining heterogeneous chemical and cell morphological patterning.

Cell mechanics and motility are responsible for collective motion of cells that result in overall deformation of epithelial tissues. On the other hand, contact-dependent cell-cell signalling is responsible for generating a large variety of intricate, self-organized, spatial patterns of the signalling molecules. Moreover, it is becoming increasingly clear that the combined mechanochemical patterns of cell shape/size and signalling molecules in the tissues, for example, in cancerous and sensory epithelium, are governed by mechanochemical coupling between chemical signalling and cell mechanics. However, a clear quantitative picture of how these two aspects of tissue dynamics, i.e., signalling and mechanics, lead to pattern and form is still emerging. Although, a number of recent experiments demonstrate that cell mechanics, cell motility, and cell-cell signalling are tightly coupled in many morphogenetic processes, relatively few modeling efforts have focused on an integrated approach. We extend the vertex model of an epithelial monolayer to account for contact-dependent signalling between adjacent cells and between non-adjacent neighbors through long protrusional contacts with a feedback mechanism wherein the adhesive strength between adjacent cells is controlled by the expression of the signalling molecules in those cells. Local changes in cell-cell adhesion lead to changes in cell shape and size, which in turn drives changes in the levels of signalling molecules. Our simulations show that even this elementary two-way coupling of chemical signalling and cell mechanics is capable of giving rise to a rich variety of mechanochemical patterns in epithelial tissues. In particular, under certain parametric conditions, bimodal distributions in cell size and shape are obtained, which resemble experimental observations in cancerous and sensory tissues.

Cluster and conquer: the morphodynamics of invasion of a compliant substrate by active rods.

The colonisation of a soft passive material by motile cells such as bacteria is common in biology. The resulting colonies of the invading cells are often observed to exhibit intricate patterns whose morphology and dynamics can depend on a number of factors, particularly the mechanical properties of the substrate and the motility of the individual cells. We use simulations of a minimal 2D model of self-propelled rods moving through a passive compliant medium consisting of particles that offer elastic resistance before being plastically displaced from their equilibrium positions. It is observed that the clustering of active (self-propelled) particles is crucial for understanding the morphodynamics of colonisation. Clustering enables motile colonies to spread faster than they would have as isolated particles. The colonisation rate depends non-monotonically on substrate stiffness with a distinct maximum at a non-zero value of substrate stiffness. This is observed to be due to a change in the morphology of clusters. Furrow networks created by the active particles have a fractal-like structure whose dimension varies systematically with substrate stiffness but is less sensitive to particle activity. The power-law growth exponent of the furrowed area is smaller than unity, suggesting that, to sustain such extensive furrow networks, colonies must regulate their overall growth rate.

Influence of interaction softness on phase separation of active particles.

Using a minimal model of active Brownian particles, we study the effect of a crucial parameter, namely the softness of the interparticle repulsion, on motility-induced phase separation. We show that an increase in particle softness reduces the ability of the system to phase separate and the system exhibits a delayed transition. After phase separation, the system state properties can be explained by a single relevant length scale, the effective interparticle distance. We estimate this length scale analytically and use it to rescale the state properties at dense phase for systems with different interaction softness. Using this length scale, we provide a scaling relation for the time taken to phase separate which shows a high sensitivity to the interaction softness.

Role of cell polarity dynamics and motility in pattern formation due to contact-dependent signalling.

A key challenge in biology is to understand how spatio-temporal patterns and structures arise during the development of an organism. An initial aggregate of spatially uniform cells develops and forms the differentiated structures of a fully developed organism. On the one hand, contact-dependent cell-cell signalling is responsible for generating a large number of complex, self-organized, spatial patterns in the distribution of the signalling molecules. On the other hand, the motility of cells coupled with their polarity can independently lead to collective motion patterns that depend on mechanical parameters influencing tissue deformation, such as cellular elasticity, cell-cell adhesion and active forces generated by actin and myosin dynamics. Although modelling efforts have, thus far, treated cell motility and cell-cell signalling separately, experiments in recent years suggest that these processes could be tightly coupled. Hence, in this paper, we study how the dynamics of cell polarity and migration influence the spatiotemporal patterning of signalling molecules. Such signalling interactions can occur only between cells that are in physical contact, either directly at the junctions of adjacent cells or through cellular protrusional contacts. We present a vertex model which accounts for contact-dependent signalling between adjacent cells and between non-adjacent neighbours through long protrusional contacts that occur along the orientation of cell polarization. We observe a rich variety of spatiotemporal patterns of signalling molecules that is influenced by polarity dynamics of the cells, relative strengths of adjacent and non-adjacent signalling interactions, range of polarized interaction, signalling activation threshold, relative time scales of signalling and polarity orientation, and cell motility. Though our results are developed in the context of Delta-Notch signalling, they are sufficiently general and can be extended to other contact dependent morpho-mechanical dynamics.

Synchronized oscillations, traveling waves, and jammed clusters induced by steric interactions in active filament arrays.

Autonomous active, elastic filaments that interact with each other to achieve cooperation and synchrony underlie many critical functions in biology. The mechanisms underlying this collective response and the essential ingredients for stable synchronization remain a mystery. Inspired by how these biological entities integrate elasticity with molecular motor activity to generate sustained oscillations, a number of synthetic active filament systems have been developed that mimic oscillations of these biological active filaments. Here, we describe the collective dynamics and stable spatiotemporal patterns that emerge in such biomimetic multi-filament arrays, under conditions where steric interactions may impact or dominate the collective dynamics. To focus on the role of steric interactions, we study the system using Brownian dynamics, without considering long-ranged hydrodynamic interactions. The simulations treat each filament as a connected chain of self-propelling colloids. We demonstrate that short-range steric inter-filament interactions and filament roughness are sufficient - even in the absence of inter-filament hydrodynamic interactions - to generate a rich variety of collective spatiotemporal oscillatory, traveling and static patterns. We first analyze the collective dynamics of two- and three-filament clusters and identify parameter ranges in which steric interactions lead to synchronized oscillations and strongly occluded states. Generalizing these results to large one-dimensional arrays, we find rich emergent behaviors, including traveling metachronal waves, and modulated wavetrains that are controlled by the interplay between the array geometry, filament activity, and filament elasticity. Interestingly, the existence of metachronal waves is non-monotonic with respect to the inter-filament spacing. We also find that the degree of filament roughness significantly affects the dynamics - specifically, filament roughness generates a locking-mechanism that transforms traveling wave patterns into statically stuck and jammed configurations. Taken together, simulations suggest that short-ranged steric inter-filament interactions could combine with complementary hydrodynamic interactions to control the development and regulation of oscillatory collective patterns. Furthermore, roughness and steric interactions may be critical to the development of jammed spatially periodic states; a spatiotemporal feature not observed in purely hydrodynamically interacting systems.

Periodic oscillations in a string of camphor infused disks.

The rhythmic beating motion of autonomously motile filaments has many practical applications. Here, we present an experimental study on a filament made of camphor infused paper disks, stitched together adjacent to each other using nylon thread. The filament displays spontaneous translatory motion when it is placed on the surface of water due to the surface tension gradients created by camphor molecules on the water surface. When this filament is clamped on one end, we obtain regular oscillatory motion instead of translation. The filament shows qualitatively different dynamics at different activity levels, which is controlled by the amount of camphor infused into the paper disks. For a better physical understanding of the filament dynamics, we develop a minimal numerical model involving a semi-flexible filament made of active polar disks, where the polarity is coupled to the instantaneous velocity of the particle. This model qualitatively reproduces different oscillatory modes of the filament. Moreover, our model reveals a rich dynamical state diagram of the system, as a function of filament activity and the coupling strength.

Aggregate morphology of active Brownian particles on porous, circular walls.

We study the motility-induced aggregation of active Brownian particles (ABPs) on a porous, circular wall. We observe that the morphology of aggregated dense-phase on a static wall depends on the wall porosity, particle motility, and the radius of the circular wall. Our analysis reveals two morphologically distinct, dense aggregates; a connected dense cluster that spreads uniformly on the circular wall and a localized cluster that breaks the rotational symmetry of the system. These distinct morphological states are similar to the macroscopic structures observed in aggregates on planar, porous walls. We systematically analyze the parameter regimes where the different morphological states are observed. We further extend our analysis to motile circular rings. We show that the motile ring propels almost ballistically due to the force applied by the active particles when they form a localized cluster, whereas it moves diffusively when the active particles form a continuous cluster. This property demonstrates the possibility of extracting useful work from a system of ABPs, even without artificially breaking the rotational symmetry.

Morphological transitions of active Brownian particle aggregates on porous walls.

Motility-induced wall aggregation of Active Brownian Particles (ABPs) is a well-studied phenomenon. Here, we study the aggregation of ABPs on porous walls, which allows the particles to penetrate through at large motility. We show that the active aggregates undergo a morphological transition from a connected dense-phase to disconnected droplets with an increase in wall porosity and the particle self-motility, similar to wetting-dewetting transitions in equilibrium fluids. We show that both morphologically distinct states are stable, and independent of initial conditions at least in some parameter regions. Our analysis reveals that changes in wall porosity affect the intrinsic properties of the aggregates and changes the effective wall-aggregate interfacial tension, consistent with the appearance of the morphological transition. Accordingly, a close analysis of the density, as well as orientational distribution, indicates that the underlying reason for such morphological transitions is not necessarily specific to the systems with porous walls, and it can be possible to observe in a larger class of confined, active systems by tuning the properties of confining walls.

Translational and rotational dynamics of a self-propelled Janus probe in crowded environments.

We computationally investigate the dynamics of a self-propelled Janus probe in crowded environments. The crowding is caused by the presence of viscoelastic polymers or non-viscoelastic disconnected monomers. Our simulations show that the translational as well as rotational mean square displacements have a distinctive three-step growth for fixed values of self-propulsion force, and steadily increase with self-propulsion, irrespective of the nature of the crowder. On the other hand, in the absence of crowders, the rotational dynamics of the Janus probe is independent of self-propulsion force. On replacing the repulsive polymers with sticky ones, translational and rotational mean square displacements of the Janus probe show a sharp drop. Since different faces of a Janus particle interact differently with the environment, we show that the direction of self-propulsion also affects its dynamics. The ratio of long-time translational and rotational diffusivities of the self-propelled probe with a fixed self-propulsion, when plotted against the area fraction of the crowders, passes through a minimum and at higher area fraction merges to its value in the absence of the crowder. This points towards the decoupling of the translational and rotational dynamics of the self-propelled probe at an intermediate area fraction of the crowders. However, such translational-rotational decoupling is absent for passive probes.

Buckling instabilities and spatio-temporal dynamics of active elastic filaments.

Biological filaments driven by molecular motors tend to experience tangential propulsive forces also known as active follower forces. When such a filament encounters an obstacle, it deforms, which reorients its follower forces and alters its entire motion. If the filament pushes a cargo, the friction on the cargo can be enough to deform the filament, thus affecting the transport properties of the cargo. Motivated by cytoskeletal filament motility assays, we study the dynamic buckling instabilities of a two-dimensional slender elastic filament driven through a dissipative medium by tangential propulsive forces in the presence of obstacles or cargo. We observe two distinct instabilities. When the filament's head is pinned or experiences significant translational but little rotational drag from its cargo, it buckles into a steadily rotating coiled state. When it is clamped or experiences both significant translational and rotational drag from its cargo, it buckles into a periodically beating, overall translating state. Using minimal analytically tractable models, linear stability theory and fully nonlinear computations, we study the onset of each buckling instability, characterize each buckled state, and map out the phase diagram of the system. Finally, we use particle-based Brownian dynamics simulations to show our main results are robust to moderate noise and steric repulsion. Overall, our results provide a unified framework to understand the dynamics of tangentially propelled filaments and filament-cargo assemblies.

Beating to rotational transition of a clamped active ribbon-like filament.

We present a detailed study of a clamped ribbon-like filament under a compressive active force using Brownian dynamics simulations. We show that a clamped ribbon-like filament is able to capture beating as well as rotational motion under the compressive force. The nature of oscillation is governed by the torsional rigidity of the filament. The frequency of oscillation is almost independent of the torsional rigidity. The beating of the filament gives a butterfly-shaped trajectory of the free-end monomer, whereas rotational motion yields a circular trajectory on a plane. The binormal correlation and the principal component analysis reveal the butterfly, elliptical, and circular trajectories of the free end monomer. We present a phase diagram for different kinds of motion in the parameter regime of compressive force and torsional rigidity.

On the growth and form of shoots.

Growing plant stems and shoots exhibit a variety of shapes that embody growth in response to various stimuli. Building on experimental observations, we provide a quantitative biophysical theory for these shapes by accounting for the inherent observed passive and active effects: (i) the active controllable growth response of the shoot in response to its orientation relative to gravity, (ii) proprioception, the shoot's growth response to its own observable current shape, and (iii) the passive elastic deflection of the shoot due to its own weight, which determines the current shape of the shoot. Our theory separates the sensed and actuated variables in a growing shoot and results in a morphospace diagram in terms of two dimensionless parameters representing a scaled local active gravitropic sensitivity, and a scaled passive elastic sag. Our computational results allow us to explain the variety of observed transient and steady morphologies with effective positive, negative and even oscillatory gravitropic behaviours, without the need for ad hoc complex spatio-temporal control strategies in terms of these parameters. More broadly, our theory is applicable to the growth of soft, floppy organs where sensing and actuation are dynamically coupled through growth processes via shape.

Flagellar dynamics of a connected chain of active, polar, Brownian particles.

We show that active, self-propelled particles that are connected together to form a single chain that is anchored at one end can produce the graceful beating motions of flagella. Changing the boundary condition from a clamp to a pivot at the anchor leads to steadily rotating tight coils. Strong noise in the system disrupts the regularity of the oscillations. We use a combination of detailed numerical simulations, mean-field scaling analysis and first passage time theory to characterize the phase diagram as a function of the filament length, passive elasticity, propulsion force and noise. Our study suggests minimal experimental tests for the onset of oscillations in an active polar chain.

Flow-induced helical coiling of semiflexible polymers in structured microchannels.

The conformations of semiflexible (bio)polymers are studied in flow-through geometrically structured microchannels. Using mesoscale hydrodynamics simulations, we show that the polymer undergoes a rod-to-helix transition as it moves from the narrow high-velocity region into the wide low-velocity region of the channel. The transient helix formation is the result of a nonequilibrium and nonstationary buckling transition of the semiflexible polymer, which is subjected to a compressive force originating from the fluid-velocity variation in the channel. The helix properties depend on the diameter ratio of the channel, the polymer bending rigidity, and the flow strength.

Semiflexible polymer conformation, distribution and migration in microcapillary flows.

The flow behavior of a semiflexible polymer in microchannels is studied using multiparticle collision dynamics, a particle-based hydrodynamic simulation technique. Conformations, distributions, and radial cross-streamline migration are investigated for various bending rigidities, with persistence lengths L(p) in the range 0.5 ≤ L(p)/L(r) ≤ 30. The flow behavior is governed by the competition between a hydrodynamic lift force and steric repulsion from the wall, which lead to migration away from the wall, and a locally varying flow induced orientation, which drives the polymer away from the channel center and towards the wall. The different dependences of these effects on the polymer bending rigidity and the flow velocity results in a complex dynamical behavior. However, a generic effect is the appearance of a maximum in the monomer and the center-of-mass distributions, which occurs at the channel center for small flow velocities, but moves off-center at higher velocities.