Viscoelastic control of spatiotemporal order in bacterial active matter.

Active matter consists of units that generate mechanical work by consuming energy1. Examples include living systems (such as assemblies of bacteria2-5 and biological tissues6,7), biopolymers driven by molecular motors8-11 and suspensions of synthetic self-propelled particles12-14. A central goal is to understand and control the self-organization of active assemblies in space and time. Most active systems exhibit either spatial order mediated by interactions that coordinate the spatial structure and the motion of active agents12,14,15 or the temporal synchronization of individual oscillatory dynamics2. The simultaneous control of spatial and temporal organization is more challenging and generally requires complex interactions, such as reaction-diffusion hierarchies16 or genetically engineered cellular circuits2. Here we report a simple technique to simultaneously control the spatial and temporal self-organization of bacterial active matter. We confine dense active suspensions of Escherichia coli cells and manipulate a single macroscopic parameter-namely, the viscoelasticity of the suspending fluid- through the addition of purified genomic DNA. This reveals self-driven spatial and temporal organization in the form of a millimetre-scale rotating vortex with periodically oscillating global chirality of tunable frequency, reminiscent of a torsional pendulum. By combining experiments with an active-matter model, we explain this behaviour in terms of the interplay between active forcing and viscoelastic stress relaxation. Our findings provide insight into the influence of bacterial motile behaviour in complex fluids, which may be of interest in health- and ecology-related research, and demonstrate experimentally that rheological properties can be harnessed to control active-matter flows17,18. We envisage that our millimetre-scale, tunable, self-oscillating bacterial vortex may be coupled to actuation systems to act a 'clock generator' capable of providing timing signals for rhythmic locomotion of soft robots and for programmed microfluidic pumping19, for example, by triggering the action of a shift register in soft-robotic logic devices20.

Design rules for controlling active topological defects.

Topological defects play a central role in the physics of many materials, including magnets, superconductors, and liquid crystals. In active fluids, defects become autonomous particles that spontaneously propel from internal active stresses and drive chaotic flows stirring the fluid. The intimate connection between defect textures and active flow suggests that properties of active materials can be engineered by controlling defects, but design principles for their spatiotemporal control remain elusive. Here, we propose a symmetry-based additive strategy for using elementary activity patterns, as active topological tweezers, to create, move, and braid such defects. By combining theory and simulations, we demonstrate how, at the collective level, spatial activity gradients act like electric fields which, when strong enough, induce an inverted topological polarization of defects, akin to a negative susceptibility dielectric. We harness this feature in a dynamic setting to collectively pattern and transport interacting active defects. Our work establishes an additive framework to sculpt flows and manipulate active defects in both space and time, paving the way to design programmable active and living materials for transport, memory, and logic.

Geometric control of topological dynamics in a singing saw.

The common handsaw can be converted into a bowed musical instrument capable of producing exquisitely sustained notes when its blade is appropriately bent. Acoustic modes localized at an inflection point are known to underlie the saw's sonorous quality, yet the origin of localization has remained mysterious. Here we uncover a topological basis for the existence of localized modes that relies on and is protected by spatial curvature. By combining experimental demonstrations, theory, and computation, we show how spatial variations in blade curvature control the localization of these trapped states, allowing the saw to function as a geometrically tunable high-quality oscillator. Our work establishes an unexpected connection between the dynamics of thin shells and topological insulators and offers a robust principle to design high-quality resonators across scales, from macroscopic instruments to nanoscale devices, simply through geometry.

Optimal transport and control of active drops.

Understanding the complex patterns in space-time exhibited by active systems has been the subject of much interest in recent times. Complementing this forward problem is the inverse problem of controlling active matter. Here, we use optimal control theory to pose the problem of transporting a slender drop of an active fluid and determine the dynamical profile of the active stresses to move it with minimal viscous dissipation. By parametrizing the position and size of the drop using a low-order description based on lubrication theory, we uncover a natural "gather-move-spread" strategy that leads to an optimal bound on the maximum achievable displacement of the drop relative to its size. In the continuum setting, the competition between passive surface tension and active controls generates richer behavior with futile oscillations and complex drop morphologies that trade internal dissipation against the transport cost to select optimal strategies. Our work combines active hydrodynamics and optimal control in a tractable and interpretable framework and begins to pave the way for the spatiotemporal manipulation of active matter.

Emergence of dynamic vortex glasses in disordered polar active fluids.

In equilibrium, disorder conspires with topological defects to redefine the ordered states of matter in systems as diverse as crystals, superconductors, and liquid crystals. Far from equilibrium, however, the consequences of quenched disorder on active condensed matter remain virtually uncharted. Here, we reveal a state of strongly disordered active matter with no counterparts in equilibrium: a dynamical vortex glass. Combining microfluidic experiments and theory, we show how colloidal flocks collectively cruise through disordered environments without relaxing the topological singularities of their flows. The resulting state is highly dynamical but the flow patterns, shaped by a finite density of frozen vortices, are stationary and exponentially degenerated. Quenched isotropic disorder acts as a random gauge field turning active liquids into dynamical vortex glasses. We argue that this robust mechanism should shape the collective dynamics of a broad class of disordered active matter, from synthetic active nematics to collections of living cells exploring heterogeneous media.

Spatial population genetics with fluid flow.

The growth and evolution of microbial populations is often subjected to advection by fluid flows in spatially extended environments, with immediate consequences for questions of spatial population genetics in marine ecology, planktonic diversity and origin of life scenarios. Here, we review recent progress made in understanding this rich problem in the simplified setting of two competing genetic microbial strains subjected to fluid flows. As a pedagogical example we focus on antagonsim, i.e., two killer microorganism strains, each secreting toxins that impede the growth of their competitors (competitive exclusion), in the presence of stationary fluid flows. By solving two coupled reaction-diffusion equations that include advection by simple steady cellular flows composed of characteristic flow motifs in two dimensions (2D), we show how local flow shear and compressibility effects can interact with selective advantage to have a dramatic influence on genetic competition and fixation in spatially distributed populations. We analyze several 1D and 2D flow geometries including sources, sinks, vortices and saddles, and show how simple analytical models of the dynamics of the genetic interface can be used to shed light on the nucleation, coexistence and flow-driven instabilities of genetic drops. By exploiting an analogy with phase separation with nonconserved order parameters, we uncover how thesegeneticdrops harness fluid flows for novel evolutionary strategies, even in the presence of number fluctuations, as confirmed by agent-based simulations as well.

Shape and size changes of adherent elastic epithelia.

Epithelial tissues play a fundamental role in various morphogenetic events during development and early embryogenesis. Although epithelial monolayers are often modeled as two-dimensional (2D) elastic surfaces, they distinguish themselves from conventional thin elastic plates in three important ways- the presence of an apical-basal polarity, spatial variability of cellular thickness, and their nonequilibrium active nature. Here, we develop a minimal continuum model of a planar epithelial tissue as an active elastic material that incorporates all these features. We start from a full three-dimensional (3D) description of the tissue and derive an effective 2D model that captures, through the curvature of the apical surface, both the apical-basal asymmetry and the spatial geometry of the tissue. Crucially, variations of active stresses across the apical-basal axis lead to active torques that can drive curvature transitions. By identifying four distinct sources of activity, we find that bulk active stresses arising from actomyosin contractility and growth compete with boundary active tensions due to localized actomyosin cables and lamellipodial activity to generate the various states spanning the morphospace of a planar epithelium. Our treatment hence unifies 3D shape deformations through the coupled mechanics of apical curvature change and in-plane expansion/contraction of substrate-adhered tissues. Finally, we discuss the implications of our results for some biologically relevant processes such as tissue folding at the onset of lumen formation.

Kirigami Mechanics as Stress Relief by Elastic Charges.

We develop a geometric approach to understand the mechanics of perforated thin elastic sheets, using the method of strain-dependent image elastic charges. This technique recognizes the buckling response of a hole under an external load as a geometrically tuned mechanism of stress relief. We use a diagonally pulled square paper frame as a model system to quantitatively test and validate our approach. Specifically, we compare nonlinear force-extension curves and global displacement fields in theory and experiment. We find a strong softening of the force response accompanied by curvature localization at the inner corners of the buckled frame. Counterintuitively, though in complete agreement with our theory, for a range of intermediate hole sizes, wider frames are found to buckle more easily than narrower ones. Upon extending these ideas to many holes, we demonstrate that interacting elastic image charges can provide a useful kirigami design principle to selectively relax stresses in elastic materials.

Defect Unbinding in Active Nematics.

We formulate the statistical dynamics of topological defects in the active nematic phase, formed in two dimensions by a collection of self-driven particles on a substrate. An important consequence of the nonequilibrium drive is the spontaneous motility of strength +1/2 disclinations. Starting from the hydrodynamic equations of active nematics, we derive an interacting particle description of defects that includes active torques. We show that activity, within perturbation theory, lowers the defect-unbinding transition temperature, determining a critical line in the temperature-activity plane that separates the quasi-long-range ordered (nematic) and disordered (isotropic) phases. Below a critical activity, defects remain bound as rotational noise decorrelates the directed dynamics of +1/2 defects, stabilizing the quasi-long-range ordered nematic state. This activity threshold vanishes at low temperature, leading to a reentrant transition. At large enough activity, active forces always exceed thermal ones and the perturbative result fails, suggesting that in this regime activity will always disorder the system. Crucially, rotational diffusion being a two-dimensional phenomenon, defect unbinding cannot be described by a simplified one-dimensional model.

Visceral organ morphogenesis via calcium-patterned muscle constrictions.

Organ architecture is often composed of multiple laminar tissues arranged in concentric layers. During morphogenesis, the initial geometry of visceral organs undergoes a sequence of folding, adopting a complex shape that is vital for function. Genetic signals are known to impact form, yet the dynamic and mechanical interplay of tissue layers giving rise to organs' complex shapes remains elusive. Here, we trace the dynamics and mechanical interactions of a developing visceral organ across tissue layers, from subcellular to organ scale in vivo. Combining deep tissue light-sheet microscopy for in toto live visualization with a novel computational framework for multilayer analysis of evolving complex shapes, we find a dynamic mechanism for organ folding using the embryonic midgut of Drosophila as a model visceral organ. Hox genes, known regulators of organ shape, control the emergence of high-frequency calcium pulses. Spatiotemporally patterned calcium pulses trigger muscle contractions via myosin light chain kinase. Muscle contractions, in turn, induce cell shape change in the adjacent tissue layer. This cell shape change collectively drives a convergent extension pattern. Through tissue incompressibility and initial organ geometry, this in-plane shape change is linked to out-of-plane organ folding. Our analysis follows tissue dynamics during organ shape change in vivo, tracing organ-scale folding to a high-frequency molecular mechanism. These findings offer a mechanical route for gene expression to induce organ shape change: genetic patterning in one layer triggers a physical process in the adjacent layer - revealing post-translational mechanisms that govern shape change.

Thermalized buckling of isotropically compressed thin sheets.

The buckling of thin elastic sheets is a classic mechanical instability that occurs over a wide range of scales. In the extreme limit of atomically thin membranes like graphene, thermal fluctuations can dramatically modify such mechanical instabilities. We investigate here the delicate interplay of boundary conditions, nonlinear mechanics, and thermal fluctuations in controlling buckling of confined thin sheets under isotropic compression. We identify two inequivalent mechanical ensembles based on the boundaries at constant strain (isometric) or at constant stress (isotensional) conditions. Remarkably, in the isometric ensemble, boundary conditions induce a novel long-ranged nonlinear interaction between the local tilt of the surface at distant points. This interaction combined with a spontaneously generated thermal tension leads to a renormalization group description of two distinct universality classes for thermalized buckling, realizing a mechanical variant of Fisher-renormalized critical exponents. We formulate a complete scaling theory of buckling as an unusual phase transition with a size-dependent critical point, and we discuss experimental ramifications for the mechanical manipulation of ultrathin nanomaterials.

Olfactory Phenotypes Differentiate Cognitively Unimpaired Seniors from Alzheimer's Disease and Mild Cognitive Impairment: A Combined Machine Learning and Traditional Statistical Approach.

BACKGROUND: Olfactory dysfunction (OD) is an early symptom of Alzheimer's disease (AD). However, olfactory testing is not commonly performed to test OD in the setting of AD. OBJECTIVE: This work investigates objective OD as a non-invasive biomarker for accurately classifying subjects as cognitively unimpaired (CU), mild cognitive impairment (MCI), and AD. METHODS: Patients with MCI (n = 24) and AD (n = 24), and CU (n = 33) controls completed two objective tests of olfaction (Affordable, Rapid, Olfactory Measurement Array -AROMA; Sniffin' Sticks Screening 12 Test -SST12). Demographic and subjective sinonasal and olfaction symptom information was also obtained. Analyses utilized traditional statistics and machine learning to determine olfactory variables, and combinations of variables, of importance for differentiating normal and disease states. RESULTS: Inability to correctly identify a scent after detection was a hallmark of MCI/AD. AROMA was superior to SST12 for differentiating MCI from AD. Performance on the clove scent was significantly different between all three groups. AROMA regression modeling yielded six scents with AUC of the ROC of 0.890 (p < 0.001). Random forest model machine learning algorithms considering AROMA olfactory data successfully predicted MCI versus AD disease state. Considering only AROMA data, machine learning algorithms were 87.5%accurate (95%CI 0.4735, 0.9968). Sensitivity and specificity were 100%and 75%, respectively with ROC of 0.875. When considering AROMA and subject demographic and subjective data, the AUC of the ROC increased to 0.9375. CONCLUSION: OD differentiates CUs from those with MCI and AD and can accurately predict MCI versus AD. Leveraging OD data may meaningfully guide management and research decisions.

Essential Oil Olfactory Test: Comparison of Affordable Rapid Olfaction Measurement Array (AROMA) to Sniffin' Sticks 12.

OBJECTIVES: To further demonstrate the validity of Affordable Rapid Olfaction Measurement Array (AROMA), an essential oil-based smell test, and compare it to the Sniffin' Sticks 12 Test (SST12). STUDY DESIGN: Prospective cross-sectional study. SETTING: Academic medical center. METHODS: Fifty healthy individuals without sinonasal disease were recruited to the study. AROMA has been previously validated against the University of Pennsylvania Smell Identification Test. The current study tests 2 additional higher concentrations to increase the ability to detect olfactory reserve. Healthy participants completed AROMA, SST12, Sino-Nasal Outcome Test (SNOT-22), and Questionnaire of Olfactory Disorders (QoD). Spearman correlations were used to evaluate AROMA, SST, SNOT-22, and QoD. RESULTS: AROMA demonstrated strong test-retest reliability (r = 0.757, P < .01). AROMA showed a moderate correlation to SST12 (ρ = 0.412, P < .01). Age and SNOT-22 were significantly correlated (P < .05) with AROMA (ρ = -0.547, -0.331, respectively), and age was weakly correlated with SST (ρ = -0.377, P < .01). Median percent correct scores were as follows: SST12 identification, 92%; AROMA detection, 90%; and AROMA identification, 81%. Median correct odor identification of AROMA concentrations at 1×, 2×, 4×, and 8× were 64%, 75%, 92%, and 92%, respectively. CONCLUSION: AROMA has a moderate correlation with SST12. AROMA is more strongly correlated than SST12 to age and SNOT-22. AROMA's stronger correlation with subjective olfactory status, low cost, and adaptability may help remove barriers to routine olfactory testing in the clinic.

Nonlinear mechanics of thin frames.

The dramatic effect kirigami, such as hole cutting, has on the elastic properties of thin sheets invites a study of the mechanics of thin elastic frames under an external load. Such frames can be thought of as modular elements needed to build any kirigami pattern. Here we develop the technique of elastic charges to address a variety of elastic problems involving thin sheets with perforations, focusing on frames with sharp corners. We find that holes generate elastic defects (partial disclinations), which act as sources of geometric incompatibility. Numerical and analytic studies are made of three different aspects of loaded frames-the deformed configuration itself, the effective mechanical properties in the form of force-extension curves, and the buckling transition triggered by defects. This allows us to understand generic kirigami mechanics in terms of a set of force-dependent elastic charges with long-range interactions.

Hidden entropy production and work fluctuations in an ideal active gas.

Collections of self-propelled particles that move persistently by continuously consuming free energy are a paradigmatic example of active matter. In these systems, unlike Brownian "hot colloids," the breakdown of detailed balance yields a continuous production of entropy at steady state, even for an ideal active gas. We quantify the irreversibility for a noninteracting active particle in two dimensions by treating both conjugated and time-reversed dynamics. By starting with underdamped dynamics, we identify a hidden rate of entropy production required to maintain persistence and prevent the rapidly relaxing momenta from thermalizing, even in the limit of very large friction. Additionally, comparing two popular models of self-propulsion with identical dissipation on average, we find that the fluctuations and large deviations in work done are markedly different, providing thermodynamic insight into the varying extents to which macroscopically similar active matter systems may depart from equilibrium.

Low-noise phase of a two-dimensional active nematic system.

We consider a collection of self-driven apolar particles on a substrate that organize into an active nematic phase at sufficiently high density or low noise. Using the dynamical renormalization group, we systematically study the two-dimensional fluctuating ordered phase in a coarse-grained hydrodynamic description involving both the nematic director and the conserved density field. In the presence of noise, we show that the system always displays only quasi-long-ranged orientational order beyond a crossover scale. A careful analysis of the nonlinearities permitted by symmetry reveals that activity is dangerously irrelevant over the linearized description, allowing giant number fluctuations to persist although now with strong finite-size effects and a nonuniversal scaling exponent. Nonlinear effects from the active currents lead to power-law correlations in the density field, thereby preventing macroscopic phase separation in the thermodynamic limit.

Probing the shear viscosity of an active nematic film.

In vitro reconstituted active systems, such as the adenosine triphosphate (ATP)-driven microtubule bundle suspension developed by the Dogic group [T. Sanchez, D. T. Chen, S. J. DeCamp, M. Heymann, and Z. Dogic, Nature (London) 491, 431 (2012)10.1038/nature11591], provide a fertile testing ground for elucidating the phenomenology of active liquid crystalline states. Controlling such novel phases of matter crucially depends on our knowledge of their material and physical properties. In this Rapid Communication, we show that the shear viscosity of an active nematic film can be probed by varying its hydrodynamic coupling to a bounding oil layer. Using the motion of disclinations as intrinsic tracers of the flow field and a hydrodynamic model, we obtain an estimate for the shear viscosity of the nematic film. Knowing this now provides us with an additional handle for robust and precision tunable control of the emergent dynamics of active fluids.