A geometrical theory of gliding motility based on cell shape and surface flow.

Gliding motility proceeds with little changes in cell shape and often results from actively driven surface flows of adhesins binding to the extracellular environment. It allows for fast movement over surfaces or through tissue, especially for the eukaryotic parasites from the phylum apicomplexa, which includes the causative agents of the widespread diseases malaria and toxoplasmosis. We have developed a fully three-dimensional active particle theory which connects the self-organized, actively driven surface flow over a fixed cell shape to the resulting global motility patterns. Our analytical solutions and numerical simulations show that straight motion without rotation is unstable for simple shapes and that straight cell shapes tend to lead to pure rotations. This suggests that the curved shapes of Plasmodium sporozoites and Toxoplasma tachyzoites are evolutionary adaptations to avoid rotations without translation. Gliding motility is also used by certain myxo- or flavobacteria, which predominantly move on flat external surfaces and with higher control of cell surface flow through internal tracks. We extend our theory for these cases. We again find a competition between rotation and translation and predict the effect of internal track geometry on overall forward speed. While specific mechanisms might vary across species, in general, our geometrical theory predicts and explains the rotational, circular, and helical trajectories which are commonly observed for microgliders. Our theory could also be used to design synthetic microgliders.

Reshaping and enzymatic activity may allow viruses to move through the mucus.

Filamentous viruses like influenza and torovirus often display systematic bends and arcs of mysterious physical origin. We propose that such viruses undergo an instability from a cylindrically symmetric to a toroidally curved state. This "toro-elastic" state emerges via spontaneous symmetry breaking under prestress due to short range spike protein interactions magnified by surface topography. Once surface stresses are sufficiently large, the filament buckles and the curved state constitutes a soft mode that can potentially propagate through the filament's material frame around a Mexican-hat-type potential. In the mucus of our airways, which constitutes a soft, porous 3D network, glycan chains are omnipresent and influenza's spike proteins are known to efficiently bind and cut them. We next show that such a non-equilibrium enzymatic reaction can induce spontaneous rotation of the curved state, leading to a whole body reshaping propulsion similar to - but different from - eukaryotic flagella and spirochetes.

The role of the nucleus for cell mechanics: an elastic phase field approach.

The nucleus of eukaryotic cells typically makes up around 30% of the cell volume and has significantly different mechanics, which can make it effectively up to ten times stiffer than the surrounding cytoplasm. Therefore it is an important element for cell mechanics, but a quantitative understanding of its mechanical role during whole cell dynamics is largely missing. Here we demonstrate that elastic phase fields can be used to describe dynamical cell processes in adhesive or confining environments in which the nucleus acts as a stiff inclusion in an elastic cytoplasm. We first introduce and verify our computational method and then study several prevalent cell-mechanical measurement methods. For cells on adhesive patterns, we find that nuclear stress is shielded by the adhesive pattern. For cell compression between two parallel plates, we obtain force-compression curves that allow us to extract an effective modulus for the cell-nucleus composite. For micropipette aspiration, the effect of the nucleus on the effective modulus is found to be much weaker, highlighting the complicated interplay between extracellular geometry and cell mechanics that is captured by our approach. We also show that our phase field approach can be used to investigate the effects of Kelvin-Voigt-type viscoelasticity and cortical tension.

Emergent conformational properties of end-tailored transversely propelling polymers.

We study the dynamics and conformations of a single active semiflexible polymer whose monomers experience a propulsion force perpendicular to the local tangent, with the end beads being different from the inner beads ("end-tailored"). Using Langevin simulations, we demonstrate that, apart from sideways motion, the relative propulsion strength between the end beads and the polymer backbone significantly changes the conformational properties of the polymers as a function of bending stiffness, end-tailoring and propulsion force. Expectedly, for slower ends the polymer curves away from the moving direction, while faster ends lead to opposite curving, in both cases slightly reducing the center of mass velocity compared to a straight fiber. Interestingly, for faster end beads there is a rich and dynamic morphology diagram: the polymer ends may get folded together to 2D loops or hairpin-like conformations that rotate due to their asymmetry in shape and periodic flapping motion around a rather straight state during full propulsion is also possible. We rationalize the simulations using scaling and kinematic arguments and present the state diagram of the conformations. Sideways propelled fibers comprise a rather unexplored and versatile class of self-propellers, and their study will open novel ways for designing, e.g. motile actuators or mixers in soft robotics.

How Influenza's Spike Motor Works.

While often believed to be a passive agent that merely exploits its host's metabolism, the influenza virus has recently been shown to actively move across glycan-coated surfaces. This form of enzymatically driven surface motility is currently not well understood and has been loosely linked to burnt-bridge Brownian ratchet mechanisms. Starting from known properties of influenza's spike proteins, we develop a physical model that quantitatively describes the observed motility. It predicts a collectively emerging dynamics of spike proteins and surface-bound ligands that combined with the virus' geometry give rise to a self-organized rolling propulsion. We show that in contrast to a Brownian ratchet, the rotary spike drive is not fluctuation driven but operates optimally as a macroscopic engine in the deterministic regime. The mechanism also applies to relatives of influenza and to man-made analogs like DNA monowheels and should give guidelines for their optimization.

Dynamics of fiberboids.

Fiberboids are active filaments trapped at the interface of two phases, able of harnessing energy (and matter) fluxes across the interface in order to produce a rolling-like self-propulsion. We discuss several table-top examples and develop the physical framework for understanding their complex dynamics. In spite of some specific features in the examples studied we conclude that the phenomenon of fiberboids is highly generic and robust across different materials, types of fluxes and timescales. Fiberboid motility should play a role from the macroscopic realm down to the micro scale and, as recently hypothesized, possibly as a means of biological self-propulsion that has escaped previous attention.

Reversible elastic phase field approach and application to cell monolayers.

Motion and generation of forces by single cells and cell collectives are essential elements of many biological processes, including development, wound healing and cancer cell migration. Quantitative wound healing assays have demonstrated that cell monolayers can be both dynamic and elastic at the same time. However, it is very challenging to model this combination with conventional approaches. Here we introduce an elastic phase field approach that allows us to predict the dynamics of elastic sheets under the action of active stresses and localized forces, e.g. from leader cells. Our method ensures elastic reversibility after release of forces. We demonstrate its potential by studying several paradigmatic situations and geometries relevant for single cells and cell monolayers, including elastic bars, contractile discs and expanding monolayers with leader cells.

Motorizing fibres with geometric zero-energy modes.

Responsive materials1-3 have been used to generate structures with built-in complex geometries4-6, linear actuators7-9 and microswimmers10-12. These results suggest that complex, fully functional machines composed solely from shape-changing materials might be possible 13 . Nonetheless, to accomplish rotary motion in these materials still relies on the classical wheel and axle motifs. Here we explore geometric zero-energy modes to elicit rotary motion in elastic materials in the absence of a rigid wheel travelling around an axle. We show that prestrained polymer fibres closed into rings exhibit self-actuation and continuous motion when placed between two heat baths due to elastic deformations that arise from rotational-symmetry breaking around the rod's axis. Our findings illustrate a simple but robust model to create active motion in mechanically prestrained objects.

Stochastic Dynamics of Nanoparticle and Virus Uptake.

The cellular uptake of nanoparticles or viruses requires that the gain of adhesion energy overcomes the cost of plasma membrane bending. It is well known that this leads to a minimal particle size for uptake. Using a simple deterministic theory for this process, we first show that, for the same radius and volume, cylindrical particles should be taken up faster than spherical particles, both for normal and parallel orientations. We then address stochastic effects, which are expected to be relevant due to small system size, and show that, now, spherical particles can have a faster uptake because the mean first passage time profits from the multiplicative noise induced by the spherical geometry. We conclude that stochastic effects are strongly geometry dependent and may favor spherical shapes during adhesion-driven particle uptake.

Why microtubules run in circles: mechanical hysteresis of the tubulin lattice.

The fate of every eukaryotic cell subtly relies on the exceptional mechanical properties of microtubules. Despite significant efforts, understanding their unusual mechanics remains elusive. One persistent, unresolved mystery is the formation of long-lived arcs and rings, e.g., in kinesin-driven gliding assays. To elucidate their physical origin we develop a model of the inner workings of the microtubule's lattice, based on recent experimental evidence for a conformational switch of the tubulin dimer. We show that the microtubule lattice itself coexists in discrete polymorphic states. Metastable curved states can be induced via a mechanical hysteresis involving torques and forces typical of few molecular motors acting in unison, in agreement with the observations.

A nonequilibrium power balance relation for analyzing dissipative filament dynamics.

Biofilaments like F-actin or microtubules, as well as cilia, flagella, or filament bundles, are often deformed by distributed and time-dependent external forces. It is highly desirable to characterize these filaments' mechanics in an efficient way, either using a single experiment or a high throughput method. We here propose a dynamic power balance approach to study nonequilibrium filament dynamics and exemplify it both experimentally and theoretically by applying it to microtubule gliding assay dynamics. Its usefulness is highlighted by the experimental determination of the lateral friction coefficient for microtubules on kinesins. In contrast to what is usually assumed, friction is anisotropic, in a similar fashion as hydrodynamic friction. We also exemplify, by considering a microtubule buckling event, that if at least one parameter is known in advance, all other parameters can be determined by analyzing a single time-dependent experiment.

Modeling crawling cell movement on soft engineered substrates.

Self-propelled motion, emerging spontaneously or in response to external cues, is a hallmark of living organisms. Systems of self-propelled synthetic particles are also relevant for multiple applications, from targeted drug delivery to the design of self-healing materials. Self-propulsion relies on the force transfer to the surrounding. While self-propelled swimming in the bulk of liquids is fairly well characterized, many open questions remain in our understanding of self-propelled motion along substrates, such as in the case of crawling cells or related biomimetic objects. How is the force transfer organized and how does it interplay with the deformability of the moving object and the substrate? How do the spatially dependent traction distribution and adhesion dynamics give rise to complex cell behavior? How can we engineer a specific cell response on synthetic compliant substrates? Here we generalize our recently developed model for a crawling cell by incorporating locally resolved traction forces and substrate deformations. The model captures the generic structure of the traction force distribution and faithfully reproduces experimental observations, like the response of a cell on a gradient in substrate elasticity (durotaxis). It also exhibits complex modes of cell movement such as "bipedal" motion. Our work may guide experiments on cell traction force microscopy and substrate-based cell sorting and can be helpful for the design of biomimetic "crawlers" and active and reconfigurable self-healing materials.

Coarse-graining the vertex model and its response to shear.

Tissue dynamics and collective cell motion are crucial biological processes. Their biological machinery is mostly known, and simulation models such as the active vertex model exist and yield reasonable agreement with experimental observations such as tissue fluidization or fingering. However, a good and well-founded continuum description for tissues remains to be developed. In this work, we derive a macroscopic description for a two-dimensional cell monolayer by coarse-graining the vertex model through the Poisson bracket approach. We obtain equations for cell density, velocity, and the cellular shape tensor. We then study the homogeneous steady states, their stability (which coincides with thermodynamic stability), and especially their behavior under an externally applied shear. Our results contribute to elucidate the interplay between flow and cellular shape. The obtained macroscopic equations present a good starting point for adding cell motion, morphogenetic, and other biologically relevant processes.

Segmental relaxations have macroscopic consequences in glassy polymer films.

We have investigated the consequences of physical aging in thin spin-coated glassy polystyrene films through detailed dewetting studies. A simultaneous and equally fast exponential decay of dewetting velocity, width, and height of the rim with aging time was observed, which is related to a reduction of residual stresses within such films. The temperature dependence of these decay times followed an Arrhenius behavior, yielding an activation energy of 70±6 kJ/mol, on the same order of magnitude as values for the ß-relaxation of polystyrene and for relaxations of surface topographical features. Our results suggest that rearrangements at the level of chain segments are sufficient to partially relax frozen-in out-of-equilibrium local chain conformations, i.e., the cause of residual stresses, and they might also be responsible for macroscopic relaxations at polymer surfaces.

Physics of self-rolling viruses.

Viruses are right at the interface of inanimate matter and life. However, recent experiments [Sakai et al., J. Virol. 92, e01522-17 (2018)0022-538X10.1128/JVI.01522-17] have shown that some influenza strains can actively roll on glycan-covered surfaces. In a previous letter [Ziebert and Kulic, Phys. Rev. Lett. 126, 218101 (2021)0031-900710.1103/PhysRevLett.126.218101] we suggested this to be a form of viral surface metabolism: a collection of spike proteins that attach to and cut the glycans act as a self-organized mechano-chemical motor. Here we study in more depth the physics of the emergent self-rolling states. We give scaling arguments how the motion arises, substantiated by a detailed analytical theory that yields the full torque-angular velocity relation of the self-organized motor. Stochastic Gillespie simulations are used to validate the theory and to quantify stochastic effects like virus detachment and reversals of its direction. Finally, we also cross-check several approximations made previously and show that the proposed mechanism is very robust. All these results point together to the statistical inevitability of viral rolling in the presence of enzymatic activity.

Optogenetic control of intracellular flows and cell migration: A comprehensive mathematical analysis with a minimal active gel model.

The actin cytoskeleton of cells is in continuous motion due to both polymerization of new filaments and their contraction by myosin II molecular motors. Through adhesion to the substrate, such intracellular flow can be converted into cell migration. Recently, optogenetics has emerged as a new powerful experimental method to control both actin polymerization and myosin II contraction. While optogenetic control of polymerization can initiate cell migration by generating protrusion, it is less clear if and how optogenetic control of contraction can also affect cell migration. Here we analyze the latter situation using a minimal variant of active gel theory into which we include optogenetic activation as a spatiotemporally constrained perturbation. The model can describe the symmetrical flow of the actomyosin system observed in optogenetic experiments, but not the long-lasting polarization required for cell migration. Motile solutions become possible if cytoskeletal polymerization is included through the boundary conditions. Optogenetic activation of contraction can then initiate locomotion in a symmetrically spreading cell and strengthen motility in an asymmetrically polymerizing one. If designed appropriately, it can also arrest motility even for protrusive boundaries.

Simple view on fingering instability of debonding soft elastic adhesives.

We study the crack-front fingering instability of an elastic adhesive tape that is peeled off a solid substrate. Our analysis is based on an energy approach using fracture mechanics and scaling laws and provides simple physical explanations for (i) the fact that the wavelength depends only on the thickness of the adhesive film and (ii) the threshold of the instability, and (iii) additionally estimates the characteristic size of the fingers. The scaling laws for these three observables are in agreement with existing experimental data.

Dewetting dynamics of stressed viscoelastic thin polymer films.

Ultrathin polymer films that are produced, e.g., by spin coating are believed to be stressed since polymers are "frozen in" into out-of-equilibrium configurations during this process. In the framework of a viscoelastic thin-film model, we study the effects of lateral residual stresses on the dewetting dynamics of the film. The temporal evolution of the height profiles and the velocity profiles inside the film as well as the dissipation mechanisms are investigated in detail. Both the shape of the profiles and the importance of frictional dissipation vs viscous dissipation inside the film are found to change in the course of dewetting. The interplay of the nonstationary profiles, the relaxing initial stress, and the changes in the dominance of the two dissipation mechanisms caused by nonlinear friction with the substrate is responsible for the rich behavior of the system. In particular, our analysis sheds a different light on the occurrence of the unexpected maximum in the rim width obtained recently in experiments on polystyrene-polydimethylsiloxane systems.

Motor-mediated alignment of microtubules in semidilute mixtures.

We propose and study a model of molecular motor-induced ordering in a cytoskeletal filament solution for the semidilute case. Motors attach to a pair of filaments and walk along the pair bringing them into closer alignment. In the semidilute regime multiple motors can bind a filament to several others and, for a critical motor density, induce a transition to an ordered phase with a nonzero mean orientation. The motors, on the one hand, cause closer filament alignment, and, on the other hand, induce fluctuations that are dependent on the relative orientation of the filaments to which the motors are attached. We develop a spatially homogenous, mean-field theory that explicitly accounts for a force-dependent detachment rate of motors, which in turn affects the mean and the fluctuations of the net force acting on a filament. This model considers each filament to be in motor contact with all other filaments in the solution. We show that the transition to the oriented state changes from second order to first order when the force-dependent detachment becomes important.