Biology subjects

Mahadevan, L.

Publications and source records attributed to Mahadevan, L..

At least 37 records · Page 2Linked to original sources

bioRxiv2022

Direct Force Measurement and Loading on Developing Tissues in Intact Avian Embryos

Developmental morphogenesis is driven by tissue stresses acting on tissue rheology. Direct measurements of forces in small tissues (100m-1mm) in situ such as in early embryos require high spatial precision and minimal invasiveness. Here we report tissue force microscopy (TiFM) integrating a vertical cantilever probe and live imaging to enable close-loop control of mechanical loading in early chicken embryos. By testing previously qualitatively characterized force-producing tissues in the elongating body axis, we show that TiFM quantitatively captures stress dynamics with high sensitivity. TiFM also provides the capacity of applying a stable, minimally-invasive and physiologically relevant load to drive tissue deformation, which alters morphogenetic progression and cell movements. Together, TiFM addresses a key technological gap in tissue force measurement and manipulation in small developing embryos, and promises to contribute to the quantitative understanding of complex multi-tissue mechanics during development.

developmental biology↗

bioRxiv2022

Active muscular hydraulics

Muscle is a complex hierarchically organized soft contractile engine. To understand the limits on the rate of contraction and muscle energetics, we construct a coarse-grained multiscale model that integrates over molecular details and describes muscle as an active sponge. Our analysis of existing experiments highlights the importance of spatially heterogeneous strains and local volumetric deformations in muscular contractions across species and muscle type. The minimal theoretical model shows how contractions generically induce intracellular fluid flow and power active hydraulic oscillations, which determine the limits of ultrafast muscular contractions. We further demonstrate that the viscoelastic response of muscle is naturally nonreciprocal - or odd - owing to its active and anisotropic nature. This points to an alternate mode of muscular power generation from periodic cycles in spatial strain alone, contrasting with previous descriptions based on temporal cycles. Our work suggests the need for a revised view of muscle dynamics that emphasizes the multiscale spatio-temporal origins of soft hydraulic power, with potential implications for physiology, biomechanics and locomotion.

biophysics↗

bioRxiv2022

Matrix viscoelasticity controls spatio-temporal tissue organization

The spatio-temporal patterning of multicellular tissues is driven by the collective dynamics of cell proliferation and active movement. These processes are mediated by the extracellular matrix environment via a combination of biomolecular and physical cues. Here we show that the passive viscoelastic properties of the matrix that encapsulate a proliferating ball of cells (e.g. a developing organoid) play a critical role in guiding tissue organization in space and time. By varying the viscoelasticity of well-defined model matrices, we show how a spheroidal tissue of breast epithelial cells breaks symmetry and forms finger-like protrusions that invade the matrix. A computational model allows us to recapitulate these observations and leads to a phase diagram that demarcates the regions of morphological stability and instability as a function of matrix viscoelasticity, tissue viscosity, cell motility and cell division rate. Experiments that use biomolecular manipulations to independently vary these parameters confirm our predictions. To further test our theory, we also study the self-organization of an in-vitro intestinal organoid and show that the morphological changes of this system also fits within our paradigm. Altogether, our studies demonstrate the role of stress relaxation mechanisms in determining the dynamics of tissue growth and the symmetry breaking instabilities associated with branching, a fundamental process in morphogenesis and oncogenesis, and suggest ways of controlling tissue form using the extracellular matrix.

biophysics↗

bioRxiv2021

Effective elasticity and persistence of strain in active filament-motor assemblies

Cross-linked composite filaments animated by molecular motors are ubiquitous in biology. An important length scale that controls the range of force transmission in these filament-motor assemblies is the distance over which elastic strain fields persist. Previous studies have identified this persistence or decay length in passive networks, and recently, in random elastic networks with embedded elements generating constant forces or stresses. Yet, the range over which strains persist in assembles comprised of motors attaching stochastically to nearly inextensible filaments remains unclear. Here, we analyze the intrinsic decay length for extensional strain in a minimal model - ordered composite assemblies comprised of cross-linked filaments interacting with arrayed motors. We explores three related concepts: the effective active elasticity of these assembles, the length scale over which localized elastic strains persist in these systems, and its dependence on motor kinetics for static and oscillatory deformations. By combining mean-field theory for noiseless weakly extensible systems with Multi-Particle Collision Brownian simulations for noisy systems we are able to additionally investigate the effects of motor noise. For steady strains, we find that the persistence length is independent of motor kinetics and dependent on the passive elasticity of the composite. For oscillatory strains, the persistence length is frequency dependent and depends on passive elasticity and on motor kinetics. For strong motor activity, the decay length is significantly modulated by extensional softening resulting from attached motors. Theoretical predictions agree qualitatively with our simulations, even at low motor numbers or moderately strong motor noise. Taken together, our results highlight how extensional strain and correlated dynamics in possess a finite range of influence even in active networks comprised of nearly inextensible filaments.

biophysics↗

bioRxiv2021

A mechanochemical model recapitulates distinct vertebrate gastrulation modes

Gastrulation is a critical event in vertebrate morphogenesis driven by cellular processes, and characterized by coordinated multi-cellular movements that form the robust morphological structures. How these structures emerge in a developing organism and vary across vertebrates remains unclear. Inspired by experiments on the chick, we derive a theoretical framework that couples actomyosin activity to tissue flow, and provides a basis for the dynamics of gastrulation morphologies. Our model predicts the onset and development of observed experimental patterns of wild-type and perturbations of chick gastrulation as a spontaneous instability of a uniform state. Varying the initial conditions and a parameter in our model, allows us to recapitulate the phase space of gastrulation morphologies seen across vertebrates, consistent with experimental observations in the accompanying paper. All together, this suggests that early embryonic self-organization follows from a minimal predictive theory of active mechano-sensitive flows.

developmental biology↗

bioRxiv2021

Viscous effects and complex local flow behaviors dominate hemolymph circulation in the living wings of locusts

An insects living systems - circulation, respiration, and a branching nervous system - extend from the body into the wing.1,2. Hemolypmh circulation in the wing is critical for hydrating tissues, such as the highly elastic resilin3 that enhances wing flexibility, and for supplying nutrients to living systems, including sensory organs such as scent-producing patches, sound-receiving tympana, and wind-sensing sensilla distributed across the wing.4-7During flight, the presence of hemolymph in the wings reduces aerodynamic instabilities like flutter8,9, and faster hemolymph flows are induced by flapping.10 Despite the critical role of hemolymph circulation in maintaining healthy wing function, wings are often considered "lifeless" cuticle, and most measurements remain qualitative or employ coarse, bulk-flow techniques. While pioneering work in the 1960s mapped hemolymph flow direction in 100 insect species,11 half a century later we still only have quantitative measurements of flow within the wings of a few insects. Here, we focused on the North American locust Schistocerca americana, a well-studied agricultural pest species, and performed a detailed, quantitative study of global and local hemolymph flows in the densely venated fore and hind wings, along with key regions in the body and pumping organs. Through high-speed fluorescent microscopy, we measured 800 individual trajectories of neutrally buoyant fluorescent particles that move in sync with hemolymph, in the wings and body of 8 live, resting locusts. Our data show that overall flow within the wings is circuitous, but local flow behavior is highly complex, with three distinct types of flow (pulsatile, continuous, and "leaky") occurring in various combinations in different areas of the wing. We provide the first quantitative measurements of "leaky" flow into wing regions that act as sinuses, where hemolymph flows out of tubular veins and pools within thin membranous regions. We also calculate Peclet, Reynolds, and Womersley numbers, and find that viscous effects dominate flow regimes throughout the wing. Pumping organs and wing regions closest to the body display significantly faster flows and higher Reynolds numbers, but remain within the viscous flow regime. Given the central role of wings in sustaining ecologically important insect behaviors such as pollination, migration, and mating, along with the vast diversity of insect wings seen in nature, this first detailed, quantitative map of hemolymph flows across a wing provides a template for future studies investigating the dynamics of hemolymph flows critical to sustaining wing health among insects.

physiology↗

bioRxiv2021

Thermoregulatory morphodynamics of honeybee clusters

During reproductive swarming, honeybees form clusters of more than 10,000 bees that hang from structures in the environment (e.g., tree branches) and are exposed to diurnal variations in ambient temperature for up to one week during the search for a new nesting site. Swarm clusters collectively modulate their morphology in response to these variations (i.e., expanding/contracting in response to heating/cooling) to maintain their internal temperature within a tolerable range and to avoid exhausting their honey stores prematurely. To understand the spatiotemporal aspects of thermoregulatory morphing, we measured the change in size and shape of swarm clusters over time and the internal temperature profiles in response to dynamic temperature ramp perturbations. We found that swarm clusters can achieve a twofold increase/decrease their volume/density when heated from 15{degrees}C to 30{degrees}C, but they do not reach an equilibrium size or shape when held at 30{degrees}C for 5 hours, long after the core temperature of the cluster has stabilized. Furthermore, the changes in cluster shape and size are hysteretic, contracting in response to cooling faster than expanding in response to heating. Although the contact diameter of the cluster increased continuously when the swarm is heated, the change in length of the swarm (base to tip) over time is non-monotonic. Consequently, the aspect ratio of the swarm fluctuated continuously even when held at a constant temperature. Taken together, our results quantify the hysteretic and anisotropic morphological responses of swarm clusters to ambient temperature variations while suggesting that both mechanical constraints and heat transfer govern the thermoregulatory morphing dynamics of swarm clusters.

animal behavior and cognition↗

bioRxiv2021

Image classification and cognition using contour curvature statistics

Although the higher order mechanisms behind object representation and classification in the visual system are still not well understood, there are hints that simple shape primitives such as "curviness" might activate neural activation and guide this process. Drawing on elementary invariance principles, we propose that a statistical geometric object, the probability distribution of the normalized contour curvatures (NCC) in the intensity field of a planar image, has the potential to represent and classify categories of objects. We show that NCC is sufficient for discriminating between cognitive categories such as animacy, size and type, and demonstrate the robustness of this metric to variation in illumination and viewpoint, consistent with neurobiological constraints and psychological experiments. A generative model for producing artificial images with the observed NCC distributions highlights the key features that our metric captures and just as importantly, those that it does not. More broadly, our study points to the need for statistical geometric approaches to cognition that build in both the statistics and the natural invariances of the sensory world.

animal behavior and cognition↗

bioRxiv2021

Ethology of morphogenesis reveals the design principles of cnidarian size and shape development

During development, organisms interact with their natural habitats while undergoing morphological changes, yet it remains unclear whether the interplay between developing systems and their environments impacts animal morphogenesis. Here, we use the cnidarian Nematostella vectensis as a developmental model to uncover a mechanistic link between organism size, shape and behavior. Using quantitative live imaging, including extensive behavioral profiling, combined with molecular and biophysical experiments, we demonstrate that the muscular hydraulic machinery that controls body movement directly drives larva-polyp morphogenesis. Unexpectedly, size and shape development are differentially controlled by antagonistic muscles. A simple theoretical model shows how a combination of slow-priming and fast-pumping pressures generated by muscular hydraulics acts as a global mechanical regulator that coordinates tissue remodeling. Altogether, our findings illuminate how dynamic behavioral modes in the environment can be harnessed to drive morphogenetic trajectories, establishing ethology as a critical component of organismal morphogenesis - termed ethology of morphogenesis.

developmental biology↗

bioRxiv2021

Cooperative escape in ants and robots

The solution of complex problems by the collective action of simple agents in both biologically evolved and synthetically engineered systems involves cooperative action. Understanding the resulting emergent solutions requires integrating across the organismal behaviors of many individuals. Here we investigate an ecologically relevant collective task in black carpenter ants Camponotus pennsylvanicus: escape from a soft, erodible confining corral. Individual ants show a transition from individual exploratory excavation at random locations to spatially localized collective exploitative excavation and escape from the corral. A minimal continuum theory that coarse-grains over individual actions and considers their integrated influence on the environment leads to the emergence of an effective phase space of behaviors in terms of excavation strength and cooperation intensity. To test the theory over the range of predicted behaviors, we used custom-built robots (RAnts) that respond to stimuli and show the emergence (and failure) of cooperative excavation and escape. Overall, our approach shows how the cooperative completion of tasks can arise from relatively simple rules that involve the interaction of simple agents with a dynamically changing environment that serves as an enabler and modulator of behavior.

animal behavior and cognition↗

bioRxiv2021

Genetic architecture of floral traits in bee- and hummingbird-pollinated sister species of Aquilegia (columbine)

Interactions with animal pollinators have helped shape the stunning diversity of flower morphologies across the angiosperms. A common evolutionary consequence of these interactions is that some flowers have converged on suites of traits, or pollination syndromes, that attract and reward specific pollinator groups. Determining the genetic basis of these floral pollination syndromes can help us understand the processes that contributed to the diversification of the angiosperms. Here, we characterize the genetic architecture of a bee-to-hummingbird pollination shift in Aquilegia (columbine) using QTL mapping of 17 floral traits encompassing color, nectar composition, and organ morphology. In this system, we find that the genetic architectures underlying differences in floral color are quite complex, and we identify several likely candidate genes involved in anthocyanin and carotenoid floral pigmentation. Most morphological and nectar traits also have complex genetic underpinnings; however, one of the key floral morphological phenotypes, nectar spur curvature, is shaped by a single locus of large effect.

plant biology↗

bioRxiv2020

Liquid condensates increase potency of amyloid fibril inhibitors

In living cells, liquid condensates form in the cytoplasm and nucleoplasm via phase separation and regulate physiological processes. They also regulate aberrant aggregation of amyloid fibrils, a process linked to Alzheimers and Parkinsons diseases. In the absence of condensates it has been shown that amyloid aggregation can be inhibited by molecular chaperones and rationally designed drugs. However it remains unknown how this drug- or chaperone-mediated inhibition of amyloid fibril aggregation is affected by phase-separated condensates. Here we study the interplay between protein aggregation, its inhibition and liquid-liquid phase separation. Our key finding is that the potency of inhibitors of amyloid formation can be strongly enhanced. We show that the corresponding mechanism relies on the colocalization of inhibitors and aggregates inside the liquid condensate. We provide experimentally testable physicochemical conditions under which the increase of inhibitor potency is most pronounced. Our work highlights the role of spatio-temporal heterogeneity in curtailing aberrant protein aggregation and suggests design principles for amyloid inhibitors accounting for partitioning of drugs into liquid condensates.

biophysics↗

bioRxiv2020

Synchronized oscillations, metachronal waves, and jammed clusters in sterically interacting active filament arrays

Autonomous active, elastic filaments that interact with each other to achieve cooperation and synchrony underlie many critical functions in biology. A striking example is ciliary arrays in the mammalian respiratory tract; here individual filaments communicate through direct interactions and through the surrounding fluid to generate metachronal traveling waves crucial for mucociliary clearance. The mechanisms underlying this collective response and the essential ingredients for stable synchronization remain a mystery. In this article, we describe Brownian dynamics simulations of multi-filament arrays, demonstrating that short-range steric inter-filament interactions and surface-roughness are sufficient to generate a rich variety of collective spatiotemporal oscillatory, traveling and static patterns. Starting from results for the collective dynamics of two- and three-filament systems, we identify parameter ranges in which inter-filament interactions lead to synchronized oscillations. We then study how these results generalize to large one-dimensional arrays of many interacting filaments. The phase space characterizing the multi-filament array dynamics and deformations exhibits rich behaviors, including oscillations and traveling metachronal waves, depending on the interplay between geometric spacing between filaments, activity, and elasticity of the filaments. Interestingly, the existence of metachronal waves is nonmonotonic with respect to the inter-filament spacing. We also find that the degree of filament surface roughness significantly affects the dynamics -- roughness on scales comparable to the filament thickness generates a locking-mechanism that transforms traveling wave patterns into statically stuck and jammed configurations. Our simulations suggest that short-ranged steric inter-filament interactions are sufficient and perhaps even critical for the development, stability and regulation of collective patterns.

biophysics↗

bioRxiv2019

Biophysical principles of choanoflagellate self-organization

Inspired by the patterns of multicellularity in choanoflagellates, the closest living relatives of animals, we quantify the biophysical processes underlying the morphogenesis of rosette colonies in the choanoflagellate Salpingoeca rosetta. We find that rosettes reproducibly transition from an early stage of 2D growth to a later stage of 3D growth, despite the underlying stochasticity of the cell lineages. We postulate that the extracellular matrix (ECM) exerts a physical constraint on the packing of proliferating cells, thereby sculpting rosette morphogenesis. Our perturbative experiments coupled with biophysical simulations demonstrates the fundamental importance of a basally-secreted ECM for rosette morphogenesis. In addition, this yields a morphospace for the shapes of these multicellular colonies, consistent with observations of a range of choanoflagellates. Overall, our biophysical perspective on rosette development complements previous genetic perspectives and thus helps illuminate the interplay between cell biology and physics in regulating morphogenesis.\n\nSignificance statementComparisons among animals and their closest living relatives, the choanoflagellates, have begun to shed light on the origin of animal multicellularity and development. Here we complement previous genetic perspectives on this process by focusing on the biophysical principles underlying colony morphology and morphogenesis. Our study reveals the crucial role of the extracellular matrix in shaping the colonies and leads to a phase diagram that delineates the range of morphologies as a function of the biophysical mechanisms at play.

biophysics↗

bioRxiv2019

Dynamic Morphoskeletons in Development

Morphogenetic flows in developmental biology are characterized by the coordinated motion of thousands of cells that organize into tissues, naturally raising the question of how this collective organization arises. Using only the Lagrangian kinematics of tissue deformation, which naturally integrates local and global mechanisms along cell paths, we can identifying the Dynamic Morphoskeletons (DM) behind morphogenesis, i.e., the evolving centerpieces of multi-cellular trajectory patterns. The DM is model and parameter-free, frame-invariant, robust to measurement errors, and can be computed from unfiltered cell velocity data. It reveals the spatial attractors and repellers of the embryo, objects that cannot be identified by simple trajectory inspection or Eulerian methods that are local and typically frame-dependent. Computing the DM underlying primitive streak formation in chicken embryo and early gastrulation in the whole fly embryo, we find that the DM captures the early footprint of known morphogenetic features, and reveals new ones, providing a geometric framework to analyze tissue organization.

developmental biology↗

bioRxiv2019

Whole genome sequencing and comparative genomic analysis reveal novel allelic variations unique to a purple colored rice landrace (Oryza sativa ssp. indica cv. Purpleputtu)

Purpleputtu (Oryza sativa ssp. indica cv. Purpleputtu) is a unique rice landrace from southern India that exhibits predominantly purple color. This study reports the underlying genetic complexity of the trait and associated domestication and de-domestication processes during its coevolution with present day cultivars. Along-with genome level allelic variations in the entire gene repertoire associated with purple, red coloration of grain and other plant parts. Comparative genomic analysis of the whole genome sequence of Purpleputtu (PP) revels total of 3,200,951 variants including 67,774 unique variations were observed in PP when compared with 108 rice genomes. Multiple sequence alignment uncovered a 14bp deletion in Rc (Red colored, a transcription factor of bHLH class) locus of PP, a key regulatory gene of anthocyanin biosynthetic pathway. Interestingly, this deletion in Rc gene is a characteristic feature of the present-day white pericarped rice cultivars. Phylogenetic analysis of Rc locus revealed a distinct clade showing proximity to the progenitor species rufipogon and nivara. In addition, PP genome exhibits a well conserved a 4.5Mbp region on chromosome 5 that harbors several loci associated with domestication of rice. Further, PP showed 1,387 unique SNPs compared to 3,024 lines of rice (SNP-Seek database). The results indicate that PP genome is rich in allelic diversity and can serve as an excellent resource for rice breeding for a variety of agronomically important traits such as disease resistance, enhanced nutritional values, stress tolerance and protection from harmful UV-B rays.

genomics↗

bioRxiv2019

Geometric probability, psychophysics and invariance

The perception of the noisy visual world around us naturally combines geometry and probability with psychophysics. So how do we perceive geometric objects from a probabilistic perspective, i.e. infer randomness in a spatial setting ? To test this psychophysically, we use a set of simple experiments to distinguish between probability distributions of planar line images connected with Buffons needle and Bertrands paradox, two classic exemplars of geometric probability. We find that participants associate greater randomness with images that are invariant under the sub-groups of translation, rotation, and scale. An information theoretic framework centered around the Radon (Hough) transform captures the observed behavioral results, and suggests that symmetry and chance are embedded in human visual perception.

neuroscience↗

bioRxiv2018

Spatiotemporal Integration in Plant Tropisms

Tropisms, growth-driven responses to environmental stimuli, cause plant organs to respond in space and time and reorient themselves. Classical experiments from nearly a century ago reveal that plant shoots respond to the integrated history of light and gravity stimuli rather than just responding instantaneously. We introduce a temporally non-local response function for the dynamics of shoot growth formulated as an integro-differential equation whose solution allows us to qualitatively reproduce experimental observations associated with intermittent and unsteady stimuli. Furthermore, an analytic solution for the case of a pulse light stimulus expresses the response function as function of experimentally tractable variables for the phototropic response of Arabidopsis hypocotyls. All together, our model enables us to predict tropic responses to time-varying stimuli, manifested in temporal integration phenomena, and sets the stage for the incorporation of additional effects such as multiple stimuli, gravitational sagging etc.

plant biology↗