Controlling inter-particle distances in crowds of motile, cognitive, active particles.

Distance control in many-particle systems is a fundamental problem in nature. This becomes particularly relevant in systems of active agents, which can sense their environment and react by adjusting their direction of motion. We employ agent-based simulations to investigate the complex interplay between agent activity, characterized by Péclet number Pe , reorientation maneuverability Ω , vision angle θ and vision range R 0 , and agent density, which determines agent distancing and dynamics. We focus on semi-dense crowds, where the vision range is much larger than the particle size. The minimal distance to the nearest neighbors, exposure time, and persistence of orientation direction are analyzed to characterize the behavior. With increasing particle speed at fixed maneuverability, particles approach each other more closely, and exhibit shorter exposure times. The temporal persistence of motion decreases with increasing Pe , reflecting the impact of activity and maneuverability on direction changes. For a vision angle θ = π / 4 , we observe the emergence of flocking aggregates with a band-like structure, somewhat reminiscent of the bands in the Vicsek model. Additionally, for vision angles θ ≥ π / 2 , several quantities are found to display a universal scaling behavior with scaling variable Pe 3 / 2 / Ω . Our results are in good agreement with recent experiments of pedestrians in confined spaces.

Collective behavior of squirmers in thin films.

Bacteria in biofilms form complex structures and can collectively migrate within mobile aggregates, which is referred to as swarming. This behavior is influenced by a combination of various factors, including morphological characteristics and propulsive forces of swimmers, their volume fraction within a confined environment, and hydrodynamic and steric interactions between them. In our study, we employ the squirmer model for microswimmers and the dissipative particle dynamics method for fluid modeling to investigate the collective motion of swimmers in thin films. The film thickness permits a free orientation of non-spherical squirmers, but constraints them to form a two-layered structure at maximum. Structural and dynamic properties of squirmer suspensions confined within the slit are analyzed for different volume fractions of swimmers, motility types (e.g., pusher, neutral squirmer, puller), and the presence of a rotlet dipolar flow field, which mimics the counter-rotating flow generated by flagellated bacteria. Different states are characterized, including a gas-like phase, swarming, and motility-induced phase separation, as a function of increasing volume fraction. Our study highlights the importance of an anisotropic swimmer shape, hydrodynamic interactions between squirmers, and their interaction with the walls for the emergence of different collective behaviors. Interestingly, the formation of collective structures may not be symmetric with respect to the two walls. Furthermore, the presence of a rotlet dipole significantly mitigates differences in the collective behavior between various swimmer types. These results contribute to a better understanding of the formation of bacterial biofilms and the emergence of collective states in confined active matter.

Clutch model for focal adhesions predicts reduced self-stabilization under oblique pulling.

Cell-matrix adhesions connect the cytoskeleton to the extracellular environment and are essential for maintaining the integrity of tissue and whole organisms. Remarkably, cell adhesions can adapt their size and composition to an applied force such that their size and strength increases proportionally to the load. Mathematical models for the clutch-like force transmission at adhesions are frequently based on the assumption that mechanical load is applied tangentially to the adhesion plane. Recently, we suggested a molecular mechanism that can explain adhesion growth under load for planar cell adhesions. The mechanism is based on conformation changes of adhesion molecules that are dynamically exchanged with a reservoir. Tangential loading drives the occupation of some states out of equilibrium, which for thermodynamic reasons, leads to the association of further molecules with the cluster, which we refer to as self-stabilization. Here, we generalize this model to forces that pull at an oblique angle to the plane supporting the cell, and examine if this idealized model also predicts self-stabilization. We also allow for a variable distance between the parallel planes representing cytoskeletal F-actin and transmembrane integrins. Simulation results demonstrate that the binding mechanism and the geometry of the cluster have a strong influence on the response of adhesion clusters to force. For oblique angles smaller than about 40∘, we observe a growth of the adhesion site under force. However this self-stabilization is reduced as the angle between the force and substrate plane increases, with vanishing self-stabilization for normal pulling. Overall, these results highlight the fundamental difference between the assumption of pulling and shearing forces in commonly used models of cell adhesion.

Motion of microswimmers in cylindrical microchannels.

Biological and artificial microswimmers often have to propel through a variety of environments, ranging from heterogeneous suspending media to strong geometrical confinement. Under confinement, local flow fields generated by microswimmers, and steric and hydrodynamic interactions with their environment determine the locomotion. We propose a squirmer-like model to describe the motion of microswimmers in cylindrical microchannels, where propulsion is generated by a fixed surface slip velocity. The model is studied using an approximate analytical solution for cylindrical swimmer shapes, and by numerical hydrodynamics simulations for spherical and spheroidal shapes. For the numerical simulations, we employ the dissipative particle dynamics method for modelling fluid flow. Both the analytical model and simulations show that the propulsion force increases with increasing confinement. However, the swimming velocity under confinement remains lower than the swimmer speed without confinement for all investigated conditions. In simulations, different swimming modes (i.e. pusher, neutral, puller) are investigated, and found to play a significant role in the generation of propulsion force when a swimmer approaches a dead end of a capillary tube. Propulsion generation in confined systems is local, such that the generated flow field generally vanishes beyond the characteristic size of the swimmer. These results contribute to a better understanding of microswimmer force generation and propulsion under strong confinement, including the motion in porous media and in narrow channels.

Wrapping anisotropic microgel particles in lipid membranes: Effects of particle shape and membrane rigidity.

Cellular engulfment and uptake of macromolecular assemblies or nanoparticles via endocytosis can be associated to both healthy and disease-related biological processes as well as delivery of drug nanoparticles and potential nanotoxicity of pollutants. Depending on the physical and chemical properties of the system, the adsorbed particles may remain at the membrane surface, become wrapped by the membrane, or translocate across the membrane through an endocytosis-like process. In this paper, we address the question of how the wrapping of colloidal particles by lipid membranes can be controlled by the shape of the particles, the particle-membrane adhesion energy, the membrane phase behavior, and the membrane-bending rigidity. We use a model system composed of soft core-shell microgel particles with spherical and ellipsoidal shapes, together with phospholipid membranes with varying composition. Confocal microscopy data clearly demonstrate how tuning of these basic properties of particles and membranes can be used to direct wrapping and membrane deformation and the organization of the particles at the membrane. The deep-wrapped states are more favorable for ellipsoidal than for spherical microgel particles of similar volume. Theoretical calculations for fixed adhesion strength predict the opposite behavior-wrapping becomes more difficult with increasing aspect ratio. The comparison with the experiments implies that the microgel adhesion strength must increase with increasing particle stretching. Considering the versatility offered by microgels systems to be synthesized with different shapes, functionalizations, and mechanical properties, the present findings further inspire future studies involving nanoparticle-membrane interactions relevant for the design of novel biomaterials and therapeutic applications.

Dynamic shapes of floppy vesicles enclosing active Brownian particles with membrane adhesion.

Recent advances in micro- and nano-technologies allow the construction of complex active systems from biological and synthetic materials. An interesting example is active vesicles, which consist of a membrane enclosing self-propelled particles, and exhibit several features resembling biological cells. We investigate numerically the behavior of active vesicles, where the enclosed self-propelled particles can adhere to the membrane. A vesicle is represented by a dynamically triangulated membrane, while the adhesive active particles are modelled as active Brownian particles (ABPs) that interact with the membrane via the Lennard-Jones potential. Phase diagrams of dynamic vesicle shapes as a function of ABP activity and particle volume fraction inside the vesicle are constructed for different strengths of adhesive interactions. At low ABP activity, adhesive interactions dominate over the propulsion forces, such that the vesicle attains near static configurations, with protrusions of membrane-wrapped ABPs having ring-like and sheet-like structures. At moderate particle densities and strong enough activities, active vesicles show dynamic highly-branched tethers filled with string-like arrangements of ABPs, which do not occur in the absence of particle adhesion to the membrane. At large volume fractions of ABPs, vesicles fluctuate for moderate particle activities, and elongate and finally split into two vesicles for large ABP propulsion strengths. We also analyze membrane tension, active fluctuations, and ABP characteristics (e.g., mobility, clustering), and compare them to the case of active vesicles with non-adhesive ABPs. The adhesion of ABPs to the membrane significantly alters the behavior of active vesicles, and provides an additional parameter for controlling their behavior.

Type-IV pili tune an adhesion-migration trade-off during surface colonization of Pseudomonas aeruginosa.

Bacterial pathogenicity relies on both firm surface adhesion and cell dissemination. How twitching bacteria resolve the fundamental contradiction between adhesion and migration is unknown. To address this question, we employ live-cell imaging of type-IV pili (T4P) and therewith construct a comprehensive mathematical model of Pseudomonas aeruginosa migration. The data show that only 10% to 50% of T4P bind to substrates and contribute to migration through random extension and retraction. Individual T4P do not display a measurable sensory response to surfaces, but their number increases on cellular surface contact. Attachment to surfaces is mediated, besides T4P, by passive adhesive forces acting on the cell body. Passive adhesions slow down cell migration and result in local random motion on short time scales, which is followed by directionally persistent, superdiffusive motion on longer time scales. Moreover, passive adhesions strongly enhance surface attachment under shear flow. Δ pilA mutants, which produce no T4P, robustly stick to surfaces under shear flow. In contrast, rapidly migrating Δ pilH cells, which produce an excessive number of T4P, are easily detached by shear. Wild-type cells sacrifice migration speed for robust surface attachment by maintaining a low number of active pili. The different cell strains pertain to disjunct regimes in a generic adhesion-migration trait space. Depending on the nature of the adhesion structures, adhesion and migration are either compatible or a trade-off is required for efficient bacterial surface colonization under different conditions.

Membrane-Mediated Interactions Between Nonspherical Elastic Particles.

The transport of particles across lipid-bilayer membranes is important for biological cells to exchange information and material with their environment. Large particles often get wrapped by membranes, a process which has been intensively investigated in the case of hard particles. However, many particles in vivo and in vitro are deformable, e.g., vesicles, filamentous viruses, macromolecular condensates, polymer-grafted nanoparticles, and microgels. Vesicles may serve as a generic model system for deformable particles. Here, we study nonspherical vesicles with various sizes, shapes, and elastic properties at initially planar lipid-bilayer membranes. Using the Helfrich Hamiltonian, triangulated membranes, and energy minimization, we predict the interplay of vesicle shapes and wrapping states. Increasing particle softness enhances the stability of shallow-wrapped and deep-wrapped states over nonwrapped and complete-wrapped states. The free membrane mediates an interaction between partial-wrapped vesicles. For the pair interaction between deep-wrapped vesicles, we predict repulsion. For shallow-wrapped vesicles, we predict attraction for tip-to-tip orientation and repulsion for side-by-side orientation. Our predictions may guide the design and fabrication of deformable particles for efficient use in medical applications, such as targeted drug delivery.

Sparse inference and active learning of stochastic differential equations from data.

Automatic machine learning of empirical models from experimental data has recently become possible as a result of increased availability of computational power and dedicated algorithms. Despite the successes of non-parametric inference and neural-network-based inference for empirical modelling, a physical interpretation of the results often remains challenging. Here, we focus on direct inference of governing differential equations from data, which can be formulated as a linear inverse problem. A Bayesian framework with a Laplacian prior distribution is employed for finding sparse solutions efficiently. The superior accuracy and robustness of the method is demonstrated for various cases, including ordinary, partial, and stochastic differential equations. Furthermore, we develop an active learning procedure for the automated discovery of stochastic differential equations. In this procedure, learning of the unknown dynamical equations is coupled to the application of perturbations to the measured system in a feedback loop. We show that active learning can significantly improve the inference of global models for systems with multiple energetic minima.

Correction: Non-equilibrium shapes and dynamics of active vesicles.

Correction for 'Non-equilibrium shapes and dynamics of active vesicles' by Priyanka Iyer et al., Soft Matter, 2022, 18, 6868-6881, https://doi.org/10.1039/D2SM00622G.

Tangentially driven active polar linear polymers-An analytical study.

The conformational and dynamical properties of isolated flexible active polar linear polymers (APLPs) are studied analytically. The APLPs are modeled as Gaussian bead-spring linear chains augmented by tangential active forces, both in a discrete and continuous representation. The polar forces lead to linear non-Hermitian equations of motion, which are solved by an eigenfunction expansion in terms of a biorthogonal basis set. Our calculations show that the polymer conformations are independent of activity. However, tangential propulsion strongly impacts the polymer dynamics and yields an active ballistic regime as well as an activity-enhanced long-time diffusive regime, which are both absent in passive systems. The polar forces imply a coupling of modes in the eigenfunction representation, in particular with the translational mode, with a respective strong influence on the polymer dynamics. The total polymer mean-square displacement on scales smaller than the radius of gyration is determined by the active internal dynamics rather than the collective center-of-mass motion, in contrast to active Brownian polymers at large Péclet numbers, reflecting the distinct difference in the propulsion mechanism.

Emergent collective behavior of active Brownian particles with visual perception.

Systems comprised of self-steering active Brownian particles are studied via simulations for a minimal cognitive flocking model. The dynamics of the active Brownian particles is extended by an orientational response with limited maneuverability to an instantaneous visual input of the positions of neighbors within a vision cone and a cut-off radius. The system exhibits large-scale self-organized structures, which depend on selected parameter values, and, in particular, the presence of excluded-volume interactions. The emergent structures in two dimensions, such as worms, worm-aggregate coexistence, and hexagonally close-packed structures, are analysed and phase diagrams are constructed. The analysis of the particle's mean-square displacement shows ABP-like dynamics for dilute systems and the worm phase. In the limit of densely packed structures, the active diffusion coefficient is significantly smaller and depends on the number of particles in the cluster. Our analysis of the cluster-growth dynamics shows distinct differences to processes in systems of short-range attractive colloids in equilibrium. Specifically, the characteristic time for the growth and decay of clusters of a particular size is longer than that of isotropically attractive colloids, which we attribute to the non-reciprocal nature of the directed visual perception. Our simulations reveal a strong interplay between ABP-characteristic interactions, such as volume exclusion and rotational diffusion, and cognitive-based interactions and navigation.

Non-equilibrium shapes and dynamics of active vesicles.

Active vesicles, constructed through the confinement of self-propelled particles (SPPs) inside a lipid membrane shell, exhibit a large variety of non-equilibrium shapes, ranging from the formation of local tethers and dendritic conformations, to prolate and bola-like structures. To better understand the behavior of active vesicles, we perform simulations of membranes modelled as dynamically triangulated surfaces enclosing active Brownian particles. A systematic analysis of membrane deformations and SPP clustering, as a function of SPP activity and volume fraction inside the vesicle is carried out. Distributions of membrane local curvature, and the clustering and mobility of SPPs obtained from simulations of active vesicles are analysed. There exists a feedback mechanism between the enhancement of membrane curvature, the formation of clusters of active particles, and local or global changes in vesicle shape. The emergence of active tension due to the activity of SPPs can well be captured by the Young-Laplace equation. Furthermore, a simple numerical method for tether detection is presented and used to determine correlations between the number of tethers, their length, and local curvature. We also provide several geometrical arguments to explain different tether characteristics for various conditions. These results contribute to the future development of steerable active vesicles or soft micro-robots whose behaviour can be controlled and used for potential applications.

Dynamics of active polar ring polymers.

The conformational and dynamical properties of isolated semiflexible active polar ring polymers are investigated analytically. A ring is modeled as a continuous Gaussian polymer exposed to tangential active forces. The analytical solution of the linear non-Hermitian equation of motion in terms of an eigenfunction expansion shows that ring conformations are independent of activity. In contrast, activity strongly affects the internal ring dynamics and yields characteristic time regimes, which are absent in passive rings. On intermediate timescales, flexible rings show an activity-enhanced diffusive regime, while semiflexible rings exhibit ballistic motion. Moreover, a second active time regime emerges on longer timescales, where rings display a snake-like motion, which is reminiscent to a tank-treading rotational dynamics in shear flow, dominated by the mode with the longest relaxation time.

Alignment and propulsion of squirmer pusher-puller dumbbells.

The properties of microswimmer dumbbells composed of pusher-puller pairs are investigated by mesoscale hydrodynamic simulations employing the multiparticle collision dynamics approach for the fluid. An individual microswimmer is represented by a squirmer, and various active-stress combinations in a dumbbell are considered. The squirmers are connected by a bond, which does not impose any geometrical restriction on the individual rotational motion. Our simulations reveal a strong influence of the squirmers' flow fields on the orientation of their propulsion directions, their fluctuations, and the swimming behavior of a dumbbell. The properties of pusher-puller pairs with an equal magnitude of the active stresses depend only weakly on the stress magnitude. This is similar to dumbbells of microswimmers without hydrodynamic interactions. However, for non-equal stress magnitudes, the active stress implies strong orientational correlations of the swimmers' propulsion directions with respect to each other, as well as the bond vector. The orientational coupling is most pronounced for pairs with large differences in the active-stress magnitude. The alignment of the squirmers' propulsion directions with respect to each other is preferentially orthogonal in dumbbells with a strong pusher and weak puller, and antiparallel in the opposite case when the puller dominates. These strong correlations affect the active motion of dumbbells, which is faster for strong pushers and slower for strong pullers.

Generic self-stabilization mechanism for biomolecular adhesions under load.

Mechanical loading generally weakens adhesive structures and eventually leads to their rupture. However, biological systems can adapt to loads by strengthening adhesions, which is essential for maintaining the integrity of tissue and whole organisms. Inspired by cellular focal adhesions, we suggest here a generic, molecular mechanism that allows adhesion systems to harness applied loads for self-stabilization through adhesion growth. The mechanism is based on conformation changes of adhesion molecules that are dynamically exchanged with a reservoir. Tangential loading drives the occupation of some states out of equilibrium, which, for thermodynamic reasons, leads to association of further molecules with the cluster. Self-stabilization robustly increases adhesion lifetimes in broad parameter ranges. Unlike for catch-bonds, bond rupture rates can increase monotonically with force. The self-stabilization principle can be realized in many ways in complex adhesion-state networks; we show how it naturally occurs in cellular adhesions involving the adaptor proteins talin and vinculin.

Erythrocyte sedimentation: Effect of aggregation energy on gel structure during collapse.

The erythrocyte (or red blood cell) sedimentation rate (ESR) is commonly interpreted as a measure of cell aggregation and as a biomarker of inflammation. It is well known that an increase of fibrinogen concentration, an aggregation-inducing protein for erythrocytes, leads to an increase of the sedimentation rate of erythrocytes, which is generally explained through the formation and faster settling of large disjoint aggregates. However, many aspects of erythrocyte sedimentation conform well with the collapse of a particle gel rather than with the sedimentation of disjoint aggregates. Using experiments and cell-level numerical simulations, we systematically investigate the dependence of ESR on fibrinogen concentration and its relation to the microstructure of the gel-like erythrocyte suspension. We show that for physiological aggregation interactions, an increase in the attraction strength between cells results in a cell network with larger void spaces. This geometrical change in the network structure occurs due to anisotropic shape and deformability of erythrocytes and leads to an increased gel permeability and faster sedimentation. Our results provide a comprehensive relation between the ESR and the cell-level structure of erythrocyte suspensions and support the gel hypothesis in the interpretation of blood sedimentation.

Erythrocyte Sedimentation: Collapse of a High-Volume-Fraction Soft-Particle Gel.

The erythrocyte sedimentation rate is one of the oldest medical diagnostic methods whose physical mechanisms remain debatable today. Using both light microscopy and mesoscale cell-level simulations, we show that erythrocytes form a soft-particle gel. Furthermore, the high volume fraction of erythrocytes, their deformability, and weak attraction lead to unusual properties of this gel. A theoretical model for the gravitational collapse is developed, whose predictions are in agreement with detailed macroscopic measurements of the interface velocity.