Active Force Dipoles Research Articles

Many-body interactions between contracting living cells.

The organization of live cells into tissues and their subsequent biological function involves inter-cell mechanical interactions, which are mediated by their elastic environment. To model this interaction, we consider cells as spherical active force dipoles surrounded by an unbounded elastic matrix. Even though we assume that this elastic medium responds linearly, each cell's regulation of its mechanical activity leads to nonlinearities in the emergent interactions between cells. We study the many-body nature of these interactions by considering several geometries that include three or more cells. We show that for different regulatory behaviors of the cells' activity, the total elastic energy stored in the medium differs from the superposition of all two-body interactions between pairs of cells within the system. Specifically, we find that the many-body interaction energy between cells that regulate their position is smaller than the sum of interactions between all pairs of cells in the system, while for cells that do not regulate their position, the many-body interaction is larger than the superposition prediction. Thus, such higher-order interactions should be considered when studying the mechanics of multiple cells in proximity.

Pair dynamics of active force dipoles in an odd-viscous fluid.

We discuss the lateral dynamics of two active force dipoles, which interact with each other via hydrodynamic interactions in a thin fluid layer that is active and chiral. The fluid layer is modeled as a two-dimensional (2D) compressible fluid with an odd viscosity, while the force dipole (representing an active protein or enzyme) induces a dipolar flow. Taking into account the momentum decay in the 2D fluid, we obtain analytically the mobility tensor that depends on the odd viscosity and includes nonreciprocal hydrodynamic interactions. We find that the particle pair shows spiral behavior due to the transverse flow induced by the odd viscosity. When the magnitude of the odd viscosity is large as compared with the shear viscosity, two types of oscillatory behaviors are seen. One of them can be understood as arising from closed orbits in dynamical systems, and its circular trajectories are determined by the ratio between the magnitude of the odd viscosity and the force dipole. In addition, the phase diagrams of the particle dipolar angles are obtained numerically. Our findings reveal that the nonreciprocal response leads to complex dynamics of active particles embedded in an active fluid with odd viscosity.

Self-induced hydrodynamic coil-stretch transition of active polymers.

We analyze the conformational dynamics and statistical properties of an active polymer model. The polymer is described as a freely jointed bead-rod chain subject to stochastic active force dipoles that act on the suspending solvent where they drive long-ranged fluid flows. Using Langevin simulations of isolated chains in unconfined domains, we show how the coupling of active flows with polymer conformations leads to emergent dynamics. Systems with contractile dipoles behave similarly to passive Brownian chains with enhanced fluctuations due to dipolar flows. In systems with extensile dipoles, however, our simulations uncover an active coil-stretch transition whereby the polymer spontaneously unfolds and stretches out in its own self-induced hydrodynamic flow, and we characterize this transition in terms of a dimensionless activity parameter comparing active dipolar forces to thermal fluctuations. We discuss our findings in the context of the classic coil-stretch transition of passive polymers in extensional flows and complement our simulations with a simple kinetic model for an active trimer.

Active Instability and Nonlinear Dynamics of Cell-Cell Junctions.

Active cell-junction remodeling is important for tissue morphogenesis, yet its underlying physics is not understood. We study a mechanical model that describes junctions as dynamic active force dipoles. Their instability can trigger cell intercalations by a critical collapse. Nonlinearities in tissue's elastic response can stabilize the collapse either by a limit cycle or condensation of junction lengths at cusps of the energy landscape. Furthermore, active junction networks undergo collective instability to drive active in-plane ordering or develop a limit cycle of collective oscillations, which extends over regions of the energy landscape corresponding to distinct network topologies.

Chaotic and periodical dynamics of active chiral droplets

The interplay between the chirality of many biological molecules and the energy injected at small length-scales as the result of biological processes is at the base of the life of the cells. With the aim of unveiling the connection between these two features, here we analyze by means of lattice Boltzmann simulations the behavior of an active droplet of cholesteric liquid crystal under the effect of intense active doping, within the framework of active gel theory. We find that a droplet of chiral liquid crystal, fueled by active force dipoles, develops defect loops (closed disclination lines) that pierce the interior of the droplet, leading the droplet to develop an erratic motility mode. When the droplet is fueled by in-warding active torque dipoles, three different dynamical regimes develops at varying both the thermodynamic chirality and the strength of active energy injection: a stable rotational state at low activity, an intermittent disclination dance regime, and a turbulent state where closed disclination lines formation is inhibited and new pairs of oppositely charged surface defects leads to the development of chaotic rotational motion. Finally, we show that out-warding torque dipoles are able to sustain a periodical dynamics at higher chirality characterized by the nucleation/annihilation of pairs of disclination rings.

Shape regulation generates elastic interaction between living cells

The organization of live cells to tissues is associated with the mechanical interaction between cells, which is mediated through their elastic environment. We model cells as spherical active force dipoles surrounded by an infinite elastic matrix, and analytically evaluate the interaction energy for different scenarios of their regulatory behavior. We obtain attraction for homeostatic (set point) forces and repulsion for homeostatic displacements. When the translational motion of the cells is regulated, the interaction energy decays with distance as , while when it is not regulated the energy decays as . This arises from the same reasons as the van der Waals interaction between induced electric dipoles.

Anomalous diffusion in viscoelastic media with active force dipoles.

With the use of the "two-fluid model," we discuss anomalous diffusion induced by active force dipoles in viscoelastic media. Active force dipoles, such as proteins and bacteria, generate nonthermal fluctuating flows that lead to a substantial increment of the diffusion. Using the partial Green's function of the two-fluid model, we first obtain passive (thermal) two-point correlation functions such as the displacement cross-correlation function between the two-point particles separated by a finite distance. We then calculate active (nonthermal) one-point and two-point correlation functions due to active force dipoles. The time correlation of a force dipole is assumed to decay exponentially with a characteristic time scale. We show that the active component of the displacement cross-correlation function exhibits various crossovers from super-diffusive to subdiffusive behaviors depending on the characteristic time scales and the particle separation. Our theoretical results are intimately related to the microrheology technique to detect fluctuations in nonequilibrium environment.

Localization and diffusion of tracer particles in viscoelastic media with active force dipoles

Optical tracking in vivo experiments reveal that diffusion of particles in biological cells is strongly enhanced in the presence of ATP and the experimental data for animal cells could previously be reproduced within a phenomenological model of a gel with myosin motors acting within it (Fodor É. et al., EPL, 110 (2015) 48005). Here, the two-fluid model of a gel is considered where active macromolecules, described as force dipoles, cyclically operate both in the elastic and the fluid components. Through coarse-graining, effective equations of motions for idealized tracer particles displaying local deformations and local fluid flows are derived. The equation for deformation tracers coincides with the earlier phenomenological model and thus confirms it. For flow tracers, diffusion enhancement caused by active force dipoles in the fluid component, and thus due to metabolic activity, is found. The latter effect may explain why ATP-dependent diffusion enhancement could also be observed in bacteria that lack molecular motors in their skeleton or when the activity of myosin motors was chemically inhibited in eukaryotic cells.

Nonequilibrium structure and dynamics in a microscopic model of thin-film active gels.

In the presence of adenosine triphosphate, molecular motors generate active force dipoles that drive suspensions of protein filaments far from thermodynamic equilibrium, leading to exotic dynamics and pattern formation. Microscopic modeling can help to quantify the relationship between individual motors plus filaments to organization and dynamics on molecular and supramolecular length scales. Here, we present results of extensive numerical simulations of active gels where the motors and filaments are confined between two infinite parallel plates. Thermal fluctuations and excluded-volume interactions between filaments are included. A systematic variation of rates for motor motion, attachment, and detachment, including a differential detachment rate from filament ends, reveals a range of nonequilibrium behavior. Strong motor binding produces structured filament aggregates that we refer to as asters, bundles, or layers, whose stability depends on motor speed and differential end detachment. The gross features of the dependence of the observed structures on the motor rate and the filament concentration can be captured by a simple one-filament model. Loosely bound aggregates exhibit superdiffusive mass transport, where filament translocation scales with lag time with nonunique exponents that depend on motor kinetics. An empirical data collapse of filament speed as a function of motor speed and end detachment is found, suggesting a dimensional reduction of the relevant parameter space. We conclude by discussing the perspectives of microscopic modeling in the field of active gels.

Cyclic Stress at mHz Frequencies Aligns Fibroblasts in Direction of Zero Strain

Recognition of external mechanical signals is vital for mammalian cells. Cyclic stretch, e.g. around blood vessels, is one such signal that induces cell reorientation from parallel to almost perpendicular to the direction of stretch. Here, we present quantitative analyses of both, cell and cytoskeletal reorientation of umbilical cord fibroblasts. Cyclic strain of preset amplitudes was applied at mHz frequencies. Elastomeric chambers were specifically designed and characterized to distinguish between zero strain and minimal stress directions and to allow accurate theoretical modeling. Reorientation was only induced when the applied stretch exceeded a specific amplitude, suggesting a non-linear response. However, on very soft substrates no mechanoresponse occurs even for high strain. For all stretch amplitudes, the angular distributions of reoriented cells are in very good agreement with a theory modeling stretched cells as active force dipoles. Cyclic stretch increases the number of stress fibers and the coupling to adhesions. We show that changes in cell shape follow cytoskeletal reorientation with a significant temporal delay. Our data identify the importance of environmental stiffness for cell reorientation, here in direction of zero strain. These in vitro experiments on cultured cells argue for the necessity of rather stiff environmental conditions to induce cellular reorientation in mammalian tissues.

Integrin adhesion drives the emergent polarization of active cytoskeletal stresses to pattern cell delamination

Tissue patterning relies on cellular reorganization through the interplay between signaling pathways and mechanical stresses. Their integration and spatiotemporal coordination remain poorly understood. Here we investigate the mechanisms driving the dynamics of cell delamination, diversely deployed to extrude dead cells or specify distinct cell fates. We show that a local mechanical stimulus (subcellular laser perturbation) releases cellular prestress and triggers cell delamination in the amnioserosa during Drosophila dorsal closure, which, like spontaneous delamination, results in the rearrangement of nearest neighbors around the delaminating cell into a rosette. We demonstrate that a sequence of "emergent cytoskeletal polarities" in the nearest neighbors (directed myosin flows, lamellipodial growth, polarized actomyosin collars, microtubule asters), triggered by the mechanical stimulus and dependent on integrin adhesion, generate active stresses that drive delamination. We interpret these patterns in the language of active gels as asters formed by active force dipoles involving surface and body stresses generated by each cell and liken delamination to mechanical yielding that ensues when these stresses exceed a threshold. We suggest that differential contributions of adhesion, cytoskeletal, and external stresses must underlie differences in spatial pattern.