Biology subjects

Prakash, M.

Publications and source records attributed to Prakash, M..

At least 55 records · Page 3Linked to original sources

bioRxiv2021

Active Sinking Particles: Sessile Suspension Feeders significantly alter the Flow and Transport to Sinking Aggregates

AO_SCPLOWBSTRACTC_SCPLOWSinking or sedimentation of biological aggregates plays a critical role in carbon sequestration in the ocean and in vertical material fluxes in waste-water treatment plants. In both these contexts, the sinking aggregates are "active," since they are biological hot-spots and are densely colonized by microorganisms including bacteria and sessile protists, some of which generate feeding currents. However, the effect of these feeding currents on the sinking rates, trajectories, and mass transfer to these "active sinking particles," has not previously been studied. Here we use a novel scale-free vertical-tracking microscope (a.k.a. Gravity Machine, Krishnamurthy et al. "Scale-free vertical tracking microscopy." Nature Methods (2020)) to follow model sinking aggregates (agar spheres) with attached protists (Vorticella convallaria), sinking over long distances while simultaneously measuring local flows. We find that activity due to attached Vorticella cause substantial changes to the flow around aggregates in a dynamic manner and reshape mass transport boundary layers. Further, we find that activity-mediated local flows along with sinking significantly changes how aggregates interact with the water-column at larger scales by modifying the encounter and plume cross-sections and by inducing sustained aggregate rotations. In this way our work suggests an important role of biological activity in understanding the growth, degradation, composition and sinking speeds of aggregates with consequences for predicting vertical material fluxes in marine, freshwater and man-made environments. 1 Significance StatementSinking aggregates are a critical part of aquatic ecosystems. Plentiful sinking aggregates account for the majority of carbon sequestration in the oceans. These aggregates are densely colonized by microorganisms, including many that generate feeding currents. Utilizing a novel instrument for high resolution imaging of sinking particles, we demonstrate that these feeding currents significantly change how water flows near the aggregates. We show that these changes in flow are likely to affect aquatic system processes, including aggregation rates, degradation rates, sinking speeds, and aggregate composition. Our work provides a starting point for exploring the larger-scale implications of attached organisms on these system processes, which, in turn, are critical for understanding carbon sequestration in the oceans or efficiency in waste-water treatment plants.

biophysics↗

bioRxiv2021

Extracellular mechanical forces drive endocardial cell volume decrease during cardiac valve morphogenesis

Organ morphogenesis involves dynamic changes of tissue properties at the cellular scale. In addition, cells need to adapt to their mechanical environment through mechanosensitive pathways. How mechanical cues influence cell behaviors during morphogenesis, however, remains poorly understood. Here we studied the influence of mechanical forces during the formation of the atrioventricular canal (AVC) where cardiac valves develop. We show that in zebrafish the AVC forms within a zone of tissue convergence between the atrium and the ventricle which is associated with increased activation of the actomyosin meshwork and endocardial cell orientation changes. We demonstrate that tissue convergence occurs with a major reduction of endocardial cell volume triggered by mechanical forces and the mechanosensitive channels TRPP2/TRPV4. In addition, we show that the extracellular matrix component hyaluronic acid controls cell volume changes. Together, our data suggest that cell volume change is a key cellular feature activated by mechanical forces during cardiovascular morphogenesis. This work further unravels how mechanical forces and extracellular matrix can influence tissue remodeling in developing organs.

developmental biology↗

bioRxiv2020

Squid: Simplifying Quantitative Imaging Platform Development and Deployment

With rapid developments in microscopy methods, highly versatile, robust and affordable implementations are needed to enable rapid and wide adoption by the biological sciences community. Here we report Squid, a quantitative imaging platform with a full suite of hardware and software components and configurations for deploying facility-grade widefield microscopes with advanced features like flat field fluorescence excitation, patterned illumination and tracking microscopy, at a fraction of the cost of commercial solutions. The open and modular nature (both in hardware and in software) lowers the barrier for deployment, and importantly, simplifies development, making the system highly configurable and experiments that can run on the system easily programmable. Developed with the goal of helping translate the rapid advances in the field of microscopy and microscopy-enabled methods, including those powered by deep learning, we envision Squid will simplify roll-out of microscopy-based applications - including at point of care and in low resource settings, make adoption of new or otherwise advanced techniques easier, and significantly increase the available microscope-hours to labs.

bioengineering↗

bioRxiv2020

Vectorchip: Microfluidic platform for highly parallel bite by bite profiling of mosquito-borne pathogen transmission

Mosquito bites transmit a number of human pathogens resulting in potentially fatal diseases including malaria, dengue, chikungunya, West Nile encephalitis, and Zika. Although female mosquitoes transmit pathogens via salivary droplets deposited during blood feeding on a host, very little is known about the genomic content of these nanoliter scale droplets, including the transmission dynamics of live pathogens. Here we introduce Vectorchip, a low-cost, scalable microfluidic platform for molecular interrogation of individual mosquito bites in a high-throughput fashion. An ultra-thin PDMS membrane coupled to a microfluidic chip acts as a biting interface, through which freely-behaving mosquitoes deposit saliva droplets by biting into isolated arrayed micro-wells enabling molecular interrogation of individual bites. By modulating membrane thickness, the device enables on-chip comparison of biting capacity and provides a mechanical filter allowing selection of a specific mosquito species. Utilizing Vectorchip, we show on-chip simultaneous detection of mosquito DNA as well as viral RNA from Zika infected Aedes aegypti mosquitoes - demonstrating multiplexed high-throughput screening of vectors and pathogens. Focus-forming assays performed on-chip quantify number of infectious viral particles transmitted during mosquito bites, enabling assessment of active virus transmission. The platform presents a promising approach for single-bite-resolution laboratory and field characterization of vector pathogen communities, to reveal the intricate dynamics of pathogen transmission, and could serve as powerful early warning artificial "sentinel" for mosquito-borne diseases.

bioengineering↗

bioRxiv2020

Plankton Planet: 'seatizen' oceanography to assess open ocean life at the planetary scale

In every liter of seawater there are between 10 and 100 billion life forms, mostly invisible, called plankton, which form the largest and most dynamic ecosystem on our planet, at the heart of global ecological and economic processes. While physical and chemical parameters of planktonic ecosystems are fairly well measured and modelled at the planetary scale, but biological data are still scarce due to the extreme cost and relative inflexibility of the classical vessels and instruments used to explore marine biodiversity. Here we introduce Plankton Planet, an initiative whose goal is to merge the creativity of researchers, makers, and mariners to (i) develop frugal scientific instrumentation and protocols to assess the genetic and morphological diversity of plankton life, and (ii) organize their systematic deployment through fleets of volunteer sailors, fishermen, or cargo-ships to generate comparable and open-access plankton data across global and long-term spatio-temporal scales. As proof-of-concept, we show how 20 crews of sailors ("planktonauts") were abl to sample plankton biomass from the world surface ocean in a single year, generating the first citizen-based, planetary dataset of plankton biodiversity based on DNA barcodes. The quality of this dataset is comparable to that generated by Tara Oceans and is not biased by the multiplication of samplers. This dataset has unveiled significant genetic novelty and can be used to explore the taxonomic and ecological diversity of plankton at both regional and global scales. This pilot project paves the way for construction of a miniaturized, modular, evolvable, affordable and open-source citizen field-platform that will allow systematic assessment of the eco/morpho/genetic variation of aquatic ecosystems across the dimensions of the Earth system.

ecology↗

bioRxiv2020

Epithelial Tissues as Active Solids: From Nonlinear Contraction Pulses to Rupture Resistance

Epithelial tissues in many contexts can be viewed as soft active solids. Their active nature is manifested in the ability of individual cells within the tissue to contract and/or remodel their mechanical properties in response to various conditions. Little is known about the emergent properties of such materials. Specifically, how an individual cellular activity gives rise to collective spatiotemporal patterns is not fully understood. Recently we reported the observation of ultrafast contraction pulses in the dorsal epithelium of T.adhaerens in vivo [1] and speculated these propagate via mechanical fields. Other accumulating evidence suggest mechanics is involved in similar contractile patterns in embryonic development in vivo and in cellular monolayers in vitro. Here we show that a widespread cellular response - activation of contraction in response to stretch - is sufficient to give rise to nonlinear propagating contraction pulses. Using a minimal numerical model and theoretical considerations we show how such mechanical pulses emerge and propagate, spontaneously or in response to external stretch. The model - whose mathematical structure resembles that of reaction-diffusion systems - explains observed phenomena in T. adhaerens (e.g. excitable or spontaneous pulses, pulse interaction) and predicts other phenomena (e.g. symmetric strain profile, "spike trains"). Finally, we show that in response to external tension, such an active two-dimensional sheet lowers and dynamically distributes the strains across its surface, hence facilitating tissue resistance to rupture. Adding a cellular softening-threshold further enhances the tissue resistance to rupture at cell-cell junctions. As cohesion is at the heart of epithelial physiology, our model may be relevant to many other epithelial systems, even if manifested at different time/length scales. SignificanceOur work demonstrates that many observed dynamical phenomena in epithelial tissues can be explained merely by mechanical cell-cell interactions, and do not require chemical diffusion or transport between cells (though chemical activity may participate in relevant intracellular processes). Specifically, we show that single cell extension-induced-contraction (EIC) is sufficient to generate propagating contraction pulses, which also increase the tissues resistance to rupture, an essential function of epithelia. Our results may shed light on how epithelial tissues function under challenging physiological conditions, e.g. in lung, gut, vasculature and other biomedical contexts. Our results may also be relevant in the study of early evolution of multicellularity and the nervous-muscular systems. Finally, the work offers guidelines for designing soft synthetic solids with improved mechanical properties.

biophysics↗

bioRxiv2020

Quantitative longitudinal predictions of Alzheimer's disease by multi-modal predictive learning

BackgroundQuantitatively predicting the progression of Alzheimers disease (AD) in an individual on a continuous scale, such as AD assessment scale-cognitive (ADAS-cog) scores, is informative for a personalized approach as opposed to qualitatively classifying the individual into a broad disease category. We hypothesize that multi-modal data and predictive learning models can be employed for longitudinally predicting ADAS-cog scores. MethodsMultivariate regression techniques were employed to model baseline multi-modal data (demographics, neuroimaging, and cerebrospinal fluid based markers, and genetic factors) and future ADAS-cog scores. Prediction models were subjected to repeated cross-validation and the resulting mean absolute error and cross-validated correlation of the model assessed. ResultsPrediction models on multi-modal data outperformed single modal data up to 36 months. Incorporating baseline ADAS-cog scores to prediction models marginally improved predictive performance. ConclusionsFuture ADAS-cog scores were successfully estimated via predictive learning aiding clinicians in identifying those at greater risk of decline and apply interventions at an earlier disease stage and inform likely future disease progression in individuals enrolled in AD clinical trials.

bioinformatics↗

bioRxiv2020

PlanktonScope: Affordable modular imaging platform for citizen oceanography

The planktonic communities within our oceans represent one of the most diverse and understudied ecosystems on the planet. A major hurdle in describing these systems is the sheer scale of the oceans along with logistical and economic constraints associated with their sampling. This is due to the limited amount of scientifically equipped fleets and affordable equipment. Here we demonstrate a modular approach for building a versatile, re-configurable imaging platform that can be adapted to a number of field applications, specifically focusing on oceanography. By using a modular hardware/software approach for building microscopes, we demonstrate high-throughput imaging of lab and field samples while enabling rapid device reconfiguration in order to match diverse applications and the evolving needs of the sampler. The presented versions of PlanktonScope are capable of autonomously imaging 1.7 ml per minute with a 1.5 {micro}m resolution, and are built with under $400 in parts. This low cost enables new applications in laboratory settings such as the continuous imaging of suspension cultures, and in-field settings with the ability to scale up for long-term deployment on an international fleet of sailing boats enabling citizens based oceanographic research

bioengineering↗

bioRxiv2020

The Taste of Blood in Mosquitoes

Blood-feeding mosquitoes survive by feeding on nectar for metabolic energy, but to develop eggs, females require a blood meal. Aedes aegypti females must accurately discriminate between blood and nectar because detection of each meal promotes one of two mutually exclusive feeding programs characterized by distinct sensory appendages, meal sizes, digestive tract targets, and metabolic fates. We investigated the role of the syringe-like blood-feeding appendage, the stylet, and discovered that sexually dimorphic stylet neurons are the first to taste blood. Using pan-neuronal GCaMP calcium imaging, we found that blood is detected by four functionally distinct classes of stylet neurons, each tuned to specific blood components associated with diverse taste qualities. Furthermore, the stylet is specialized to detect blood over nectar. Stylet neurons are insensitive to nectar-specific sugars and responses to glucose, the sugar found in both blood and nectar, depend on the presence of additional blood components. The distinction between blood and nectar is therefore encoded in specialized neurons at the very first level of sensory detection in mosquitoes. This innate ability to recognize blood is the basis of vector-borne disease transmission to millions of people world-wide.

neuroscience↗

bioRxiv2020

BiteOscope: an open platform to study mosquito blood-feeding behavior

Female mosquitoes need a blood meal to reproduce, and in obtaining this essential nutrient they transmit deadly pathogens. Although crucial for the spread of mosquito-borne diseases, our understanding of skin exploration, probing, and engorgement, is limited due to a lack of quantitative tools. Indeed, studies often expose human subjects to assess biting behavior. Here, we present the biteOscope, a device that attracts mosquitoes to a host mimic which they bite to obtain an artificial blood meal. The host mimic is transparent, allowing high-resolution imaging of the feeding mosquito. Using machine learning we extract detailed behavioral statistics describing the locomotion, pose, biting, and feeding dynamics of Aedes aegypti, Aedes albopictus, Anopheles stephensi, and Anopheles coluzzii. In addition to characterizing behavioral patterns, we discover that the common insect repellent DEET repels Anopheles coluzzii upon contact with their legs. The biteOscope provides a new perspective on mosquito blood feeding, enabling high-throughput quantitative characterization of the effects physiological and environmental factors have on this lethal behavior.

animal behavior and cognition↗

bioRxiv2019

Regionalized tissue fluidization by an actomyosin cable is required for epithelial gap closure during insect gastrulation

Many animal embryos pull and close an epithelial sheet around the spherical or ellipsoidal egg surface during a gastrulation process known as epiboly. The ovoidal geometry dictates that the epithelial sheet first expands and subsequently compacts. Moreover, the epithelial sheet spreading over the sphere is mechanically stressed and this stress needs to be released. Here we show that during extraembryonic tissue (serosa) epiboly in the red flour beetle Tribolium castaneum, the non-proliferative serosa becomes regionalized into two distinct territories: a dorsal region under higher tension away from the leading edge with larger non-rearranging cells, and a more fluid ventral region under lower tension surrounding the leading edge with smaller cells undergoing cell intercalation. Our results suggest that fluidization of the leading edge is caused by a heterogeneous actomyosin cable that drives sequential eviction and intercalation of individual cells away from the serosa margin. Since this developmental solution utilized during epiboly resembles the mechanism of wound healing in other systems, we propose actomyosin cable-driven local tissue fluidization as a conserved morphogenetic module for closure of epithelial gaps.

developmental biology↗

bioRxiv2019

Restoring Function After Severe Spinal Cord Injury Through Bioluminescence-Driven Optogenetics

The ability to manipulate specific neuronal populations of the spinal cord following spinal cord injury (SCI) could prove highly beneficial for rehabilitation in patients through maintaining and strengthening still existing neuronal connections and/or facilitating the formation of new connections. A non-invasive and highly specific approach to neuronal stimulation is bioluminescent-optogenetics (BL-OG), where genetically expressed light emitting luciferases are tethered to light sensitive channelrhodopsins (luminopsins, LMO); neurons are activated by the addition of the luciferase substrate coelenterazine (CTZ). This approach utilizes ion channels for current conduction while activating the channels through application of a small chemical compound, thus allowing non-invasive stimulation and recruitment of all targeted neurons. Rats were transduced in the lumbar spinal cord with AAV2/9 to express the excitatory LMO3 under control of a pan-neuronal or motor neuron-specific promoter. A day after contusion injury of the thoracic spine, rats received either CTZ or vehicle every other day for 2 weeks. Activation of either interneuron or motor neuron populations below the level of injury significantly improved locomotor recovery lasting beyond the time of stimulation. Utilizing histological and gene expression methods we identified neuronal plasticity as a likely mechanism underlying the functional recovery. These findings provide a foundation for a rational approach to spinal cord injury rehabilitation, thereby advancing approaches for functional recovery after SCI.

neuroscience↗

bioRxiv2019

Octopi: Open configurable high-throughput imaging platform for infectious disease diagnosis in the field

AO_SCPLOWBSTRACTC_SCPLOWAccess to quantitative, robust, yet affordable diagnostic tools is necessary to reduce global infectious disease burden. Manual microscopy has served as a bedrock for diagnostics with wide adaptability, although at a cost of tedious labor and human errors. Automated robotic microscopes are poised to enable a new era of smart field microscopy but current platforms remain cost prohibitive and largely inflexible, especially for resource poor and field settings. Here we present Octopi, a low-cost ($250-$500) and reconfigurable autonomous microscopy platform capable of automated slide scanning and correlated bright-field and fluorescence imaging. Being highly modular, it also provides a framework for new disease-specific modules to be developed. We demonstrate the power of the platform by applying it to automated detection of malaria parasites in blood smears. Specifically, we discovered a spectral shift on the order of 10 nm for DAPI-stained Plasmodium falciparum malaria parasites. This shift allowed us to detect the parasites with a low magnification (equivalent to 10x) large field of view (2.56 mm2) module. Combined with automated slide scanning, real time computer vision and machine learning-based classification, Octopi is able to screen more than 1.5 million red blood cells per minute for parasitemia quantification, with estimated diagnostic sensitivity and specificity exceeding 90% at parasitemia of 50/ul and 100% for parasitemia higher than 150/l. With different modules, we further showed imaging of tissue slice and sputum sample on the platform. With roughly two orders of magnitude in cost reduction, Octopi opens up the possibility of a large robotic microscope network for improved disease diagnosis while providing an avenue for collective efforts for development of modular instruments.\n\nOne sentence summaryWe developed a low-cost ($250-$500) automated imaging platform that can quantify malaria parasitemia by scanning 1.5 million red blood cells per minute.

bioengineering↗

bioRxiv2019

Motility induced fracture reveals a ductile to brittle crossover in the epithelial tissues of a simple animal

Animals are characterized by their movement, and their tissues are continuously subjected to dynamic force loading while they crawl, walk, run or swim1. Tissue mechanics fundamentally determine the ecological niches that can be endured by a living organism2. While epithelial tissues provide an important barrier function in animals, they are subjected to extreme strains during day to day physiological activities, such as breathing1, feeding3, and defense response4. How-ever, failure or inability to withstand to these extreme strains can result in epithelial fractures5, 6 and associated diseases7, 8. From a materials science perspective, how properties of living cells and their interactions prescribe larger scale tissue rheology and adaptive response in dynamic force landscapes remains an important frontier9. Motivated by pushing tissues to the limits of their integrity, we carry out a multi-modal study of a simple yet highly dynamic organism, the Trichoplax Adhaerens10-12, across four orders of magnitude in length (1 {micro}m to 10 mm), and six orders in time (0.1 sec to 10 hours). We report the discovery of abrupt, bulk epithelial tissue fractures ([~]10 sec) induced by the organisms own motility. Coupled with rapid healing ([~]10 min), this discovery accounts for dramatic shape change and physiological asexual division in this early-divergent metazoan. We generalize our understanding of this phenomena by codifying it in a heuristic model, highlighting the fundamental questions underlying the debonding/bonding criterion in a soft-active-living material by evoking the concept of an epithelial alloy. Using a suite of quantitative experimental and numerical techniques, we demonstrate a force-driven ductile to brittle material transition governing the morphodynamics of tissues pushed to the edge of rupture. This work contributes to an important discussion at the core of developmental biology13-17, with important applications to an emerging paradigm in materials and tissue engineering5, 18-20, wound healing and medicine8, 21, 22.

biophysics↗

bioRxiv2019

Multi-scale spatial heterogeneity enhances particle clearance in airway ciliary arrays

Mucus clearance constitutes the primary defence of the respiratory system against viruses, bacteria and environmental insults [1]. This transport across the entire airway emerges from the integrated activity of thousands of multiciliated cells, each containing hundreds of cilia, which together must coordinate their spatial arrangement, alignment and motility [2, 3]. The mechanisms of fluid transport have been studied extensively at the level of an individual cilium [4, 5], collectively moving metachronal waves [6-10], and more generally the hydrodynamics of active matter [11, 12]. However, the connection between local cilia architecture and the topology of the flows they generate remains largely unexplored. Here, we image the mouse airway from the sub-cellular (nm) to the organ scales (mm), characterising quantitatively its ciliary arrangement and the generated flows. Locally we measure heterogeneity in both cilia organisation and flow structure, but across the trachea fluid transport is coherent. To examine this result, a hydrodynamic model was developed for a systematic exploration of different tissue architectures. Surprisingly, we find that disorder enhances particle clearance, whether it originates from fluctuations, heterogeneity in multiciliated cell arrangement or ciliary misalignment. This resembles elements of stochastic resonance [13-15] in a self-assembled biological system. Taken together, our results shed light on how the microstructure of an active carpet [16, 17] determines its emergent dynamics. Furthermore, this work is also directly applicable to human airway pathologies [1], which are the third leading cause of deaths worldwide [18].

biophysics↗

bioRxiv2019

Scale-free Vertical Tracking Microscopy: Towards Bridging Scales in Biological Oceanography

Understanding key biophysical phenomena in the ocean often requires one to simultaneously focus on microscale entities, such as motile plankton and sedimenting particles, while maintaining the macroscale context of vertical transport in a highly stratified environment. This poses a conundrum: How to measure single organisms, at microscale resolution, in the lab, while allowing them to freely move hundreds of meters in the vertical direction? We present a solution in the form of a scale-free, vertical tracking microscope based on a circular \"hydrodynamic-treadmill\". Our technology allows us to transcend physiological and ecological scales, tracking organisms from marine zooplankton to single-cells over vertical scales of meters while resolving microflows and behavioral processes. We demonstrate measurements of sinking particles, including marine snow as they sediment tens of meters while capturing sub-particle-scale phenomena. We also demonstrate depth-patterned virtual-reality environments for novel behavioral analyses of microscale plankton. This technique offers a new experimental paradigm in microscale ocean biophysics by combining physiological-scale imaging with free movement in an ecological-scale patterned environment.\n\nOne sentence summaryScale-free vertical tracking microscopy captures, for the first time, untethered behavioral dynamics at cellular resolution for marine plankton.

biophysics↗

bioRxiv2018

Collective intercellular communication through ultra-fast hydrodynamic trigger waves

The biophysical relationships between sensors and actuators [1-5] have been fundamental to the development of complex life forms; Abundant flows are generated and persist in aquatic environments by swimming organisms [6-13], while responding promptly to external stimuli is key to survival [14-19]. Here, akin to a chain reaction [20-22], we present the discovery of hydrodynamic trigger waves in cellular communities of the protist Spirostomum ambiguum, propagating hundreds of times faster than the swimming speed. Coiling its cytoskeleton, Spirostomum can contract its long body by 50% within milliseconds [23], with accelerations reaching 14g-forces. Surprisingly, a single cellular contraction (transmitter) is shown to generate long-ranged vortex flows at intermediate Reynolds numbers, which can trigger neighbouring cells, in turn. To measure the sensitivity to hydrodynamic signals (receiver), we further present a high-throughput suction-flow device to probe mechanosensitive ion channel gating [24] by back-calculating the microscopic forces on the cell membrane. These ultra-fast hydrodynamic trigger waves are analysed and modelled quantitatively in a universal framework of antenna and percolation theory [25, 26]. A phase transition is revealed, requiring a critical colony density to sustain collective communication. Our results suggest that this signalling could help organise cohabiting communities over large distances, influencing long-term behaviour through gene expression, comparable to quorum sensing [16]. More immediately, as contractions release toxins [27], synchronised discharges could also facilitate the repulsion of large predators, or conversely immobilise large prey. We postulate that beyond protists numerous other freshwater and marine organisms could coordinate with variations of hydrodynamic trigger waves.

biophysics↗

bioRxiv2018

Coupled active systems encode emergent behavioral dynamics of the unicellular predator Lacrymaria olor

Multiple active systems in a cell work together to produce sophisticated cellular behaviors such as motility and search. However, it is often unclear how this coupling specifies the complex emergent dynamics that define such behaviors. As a model system, we analyzed the hunting strategy of Lacrymaria olor, a unicellular predatory ciliate that uses extreme morphological changes to extend, contract and whip an apparent \"cell neck\" over many body lengths to capture prey. Tracking millions of unique subcellular morphologies over time revealed that these fast dynamics encode a comprehensive local search behavior apparent only at longer timescales. This hunting behavior emerges as a tug-of-war between active sub-cellular structures that use surface cilia and cortex contractility to deform the structure of the neck. The resulting search space can be described mathematically using a small number of normal shape modes that change amplitude rapidly during hunts. The distribution of these shape modes in space and time reveals a transition point between tense and compressed neck morphologies at the mean neck length, such that new shapes are readily sampled by repeatedly extending and retracting across this critical length. Molecular perturbations to the cell-signaling controller show that coupling between ciliary and contractile programs is needed to maintain this length/shape relationship; neither system alone provides the dynamic repertoire of shapes necessary for comprehensive search. Our results highlight the utility of coupling antagonistic active systems as a strategy for encoding or engineering complex behaviors in molecular machines.\n\nOne Sentence Summary: Analysis of millions of unique cellular morphologies of the highly dynamic single-celled predator Lacrymaria olor reveals that it programs a comprehensive search space and emergent hunting behavior through coupling surface based active cilia and cortex based contractile molecular systems together.

systems biology↗