Biology subjects

Mahadevan, L.

Publications and source records attributed to Mahadevan, L..

At least 19 recordsLinked to original sources

bioRxiv2026

How spiders use dragline silk to control abseiling and jumping

Spiders arrest their fall by abseiling on dragline silk, varying silk release rate to avoid excessive strains that could break the thread. To understand how this is achieved, we develop a minimal dynamical model of abseiling and formulate a time-optimal control problem subject to physical limits on silk strain and dragline spinning rate. We find that the optimal trajectory includes an interval over which the strain is constant, resulting in uniform deceleration consistent with published experiments. To test the generality of this strategy, we then turn to a distinct extreme motor behavior seen in jumping spiders: using a dragline anchored at the takeoff site to correct their orientation while jumping at speeds exceeding 100 body lengths per second. We show that the same constant-strain strategy suffices to counteract the initial body rotation and ensure an upright landing without significant loss of range. Together, our theoretical framework suggests how strain regulation may serve as a strategy for controlling extreme movements such as abseiling seen in many spiders and may be specialized to tasks such as aerial braking and reorientation in jumping spiders.

animal behavior and cognition↗

bioRxiv2026

Modeling one-shot interceptions in fruit-catching fish

Interception of moving objects is a universal pattern of animal behavior with many industrial applications. Inspired by the behavior of the characid fish Brycon guatemalensis, which catches fruits falling onto the surface of a river, we study one-shot (i.e., open-loop) interceptions using both stochastic optimal control theory and reinforcement learning. In the first instance, an agent actuates a control (wait time before launch and heading angle) to meet its target, given a noisy estimate of the target initial state. In a minimal setting, where launch velocity and actuated control are constants, we show that the optimal wait time is attenuated by noise in both the target measurement and control actuation, as well as agent energy conservation. We then derive an upper bound for the heading angle variance which scales as the ratio of the non-vanishing optimal interception error to the initial planar separation. Complementing our control framework, our deep reinforcement learning approach shows that the neural network representing the fish first learns the value function for the interception, then learns how to aim, and finally learns the optimal wait time. Beyond the specific problem at hand, our results may also have applications to problems with little time for feedback or corrections such as perching, landing, and docking.

animal behavior and cognition↗

bioRxiv2026

Parametric Engineering of Atrioventricular Living Valve Transplants

Diseases of the (mitral and tricuspid) atrioventricular valves (AVV), which regulate inflow from the atria to the ventricles, can result in severe obstruction to inflow (stenosis) or valvular leakage (regurgitation), requiring surgical intervention. In patients with small annulus diameters (< 19 mm), valve replacement is a clinical challenge limited by prosthesis size constraints, lack of growth potential, suboptimal durability, and elevated thrombosis and bleeding risk. While living valve transplantation (LVT) has re-opened the possibility of using allogeneic valve tissue capable of growth and remodeling, translating this to the AVV has been challenging given the anatomical complexity of the sub-valvular apparatus. Here, we propose a strategy using a replacement bi-leaflet cylindrical valve fabricated from donor AVV tissue and artificial chordae, with a geometry designed to mimic the native AVV and engineered to satisfy predefined clinical targets. Pulse duplicator experiments allowed characterization of valve dynamics in terms of clinically important attributes framed as dimensionless parameters. A multi-objective optimization allowed us to identify an optimal design which we implemented in porcine AVV replacements (n=6). Our results demonstrated favorable hemodynamics with minimal regurgitation and stenosis, suggesting a promising method for patient-optimized valve replacements.

bioengineering↗

bioRxiv2026

Substrate mediated mechanical forces enable optimal kinetic proofreading by T-cell receptors

T-cells use molecular reactions with nonequilibrium error correction, i.e., proofreading, to discriminate between nearly identical antigens with high specificity and sensitivity. These receptor binding events are known to be force sensitive, yet traditional schemes of proofreading focus on reaction kinetics alone and do not consider the role of force dependent catch/slip bond behavior or interactions with mechanically engaged coreceptors such as adhesion molecules. To address this, we propose a minimal framework for proofreading of ligand discrimination by T-cell receptors (TCRs) that uses endogenous TCR mechanosensation and substrate-mediated mechanical interactions with adhesive proteins (load sharing) to improve recognition fidelity. We leverage the catch bond behavior of cognate antigens to delay decision making and amplify TCR signaling while discarding noncognate slip bond ligands in the presence of a force. By integrating our model with existing structural and molecular data, we show that substrate mechanics regulates the transmission of active cytoskeletal forces through a molecular clutch and controls the energization of bound TCRs needed for optimal proofreading. Our work demonstrates how mechanical forces and substrate properties can augment kinetic proofreading in T-cells, suggesting biomaterial design strategies for immunotherapies that tune the mechanical microenvironment of T-cells to achieve high fidelity TCR-ligand discrimination, antigen recognition, and activation.

biophysics↗

bioRxiv2025

Optimal bioelectric control accelerates collective wound healing

Collective cell migration is critical in a range of biophysical processes spanning wound healing to tumor metastasis. It is therefore important to develop techniques for regulating cell motion, but while we have developed powerful migration tools from optogenetics and bioelectricity, the complex mechanics of collective systems make it difficult to determine where and when to apply these stimuli. For example, here we begin with a circular sheet of skin cells with a central hole, or "wound", and show that globally stimulating all cells to migrate radially inwards to close the gap through electrotaxis causes catastrophic mechanical damage, emerging from strong cell-cell adhesion, which we explain with an active elasticity model. We propose a solution inspired by sheepherding based on using local stimulation to learn the collective perturbation-response of the group and then drive tissue motion. First, we induce local electrotaxis to characterize the impulse-response function of quasi-1D strips of skin tissue, discovering that hyper-local stimulation triggers long-range tissue response over a length scale set by cell-cell adhesion also predicted by our model. Based on this, we apply local, concentric ring fields to in vitro circular wounds. Continuously driving cells towards the wound core kinetically traps the tissue in a jammed state and freezes healing. Pulsing the stimuli allows the tissue to relax and fluidize again, accelerating migration. Finally, we integrate the key length and timescales of tissue mechanics into a biophysically-informed continuum control model. The models predictive framework helps determine where and when to apply stimulation for optimal tissue growth which, when tested, accelerates healing 5-fold.

biophysics↗

bioRxiv2025

Distributed neural computation and the evolution of the first brains

The origin of brains in the Precambrian was a landmark in animal evolution, enabling new behavior and life histories. Brains likely evolved from diffuse nerve nets, but we do not know what the first brains looked like or how they were organized. Acoel worms, the likely sister lineage to all other animals with brains, offer a unique window into this transition. Here, we studied the acoel worm Hofstenia miamia, a marine predator that hunts planktonic invertebrates and displays other sophisticated behavior. We found that H. miamia has an unusual diffuse brain: a subepidermal network of dense neuropil exhibiting little regionalization or stereotypy in gross anatomy or distribution of neural cell types. Remarkably, we found that behavior in H. miamia is robust to large, arbitrary amputations of brain regions, suggesting that most regions can perform most computations. More brain tissue improves performance, especially on challenging tasks, but no specific brain region is required. These results lead us to propose that H. miamias brain is composed of computationally pluripotent "tiles" that interact to generate coherent behavior. This architecture suggests a trajectory for nervous system evolution in which early brains may have arisen through the condensation of diffuse nerve nets into unregionalized brains, with regionalization evolving secondarily.

neuroscience↗

bioRxiv2025

Reversible superdeformability of hiPSC epithelial cortinoids

Epithelial cortinoids, fluid filled shells formed from induced pluripotent stem cells (iPSCs), must accommodate large deformations during growth and morphogenesis. Using inflation-deflation assays and high-resolution imaging, we find that these fluid-filled shells are weakly-pressurized and achieve extreme deformability through reversible soft modes of deformation accommodated by the cytoskeleton. We show that cytoskeletal elements such as actin localized along lateral cell edges undergo tilt and bend instabilities that buffer mechanical load by decoupling apico-basal stretching from lateral extension. These reversible instabilities act as elastic safety valves, permitting large shape changes without loss of epithelial hydraulic and topological integrity. A minimal theoretical and computational model demonstrates how tilt and bend reduce effective resistance to radial thinning and explains the observed pressure-strain softening. Thus, iPSC shells exploit reversible cytoskeletal instabilities as mechanical buffers, enabling robust tolerance of large deformations in developing epithelia.

biophysics↗

bioRxiv2025

Morphogenesis and morphometry of brain folding patterns across species

Evolutionary adaptations associated with the formation of a folded cortex in many mammalian brains are thought to be a critical specialization associated with higher cognitive function. The dramatic surface expansion and highly convoluted folding of the cortex during early development is a theme with variations that suggest the need for a comparative study of cortical gyrification. Here, we use a combination of physical experiments using gels, computational morphogenesis, and geometric morphometrics to study the folding of brains across different species. Starting with magnetic resonance images of brains of a newborn ferret, a fetal macaque, and a fetal human, we construct two-layer physical gel brain models that swell superficially in a solvent, leading to folding patterns similar to those seen in vivo. We then adopt a three-dimensional continuum model based on differential growth to simulate cortical folding in silico. Finally, we deploy a comparative morphometric analysis of the in vivo, in vitro, and in silico surface buckling patterns across species. Our study shows that a simple mechanical instability driven by differential growth suffices to explain cortical folding and suggests that variations in the tangential growth and different initial geometries are sufficient to explain the differences in cortical folding across species.

neuroscience↗

bioRxiv2025

Biophysical basis for brain folding and misfolding patterns in ferrets and humans

A mechanistic understanding of neurodevelopment requires us to follow the multiscale processes that connect molecular genetic processes to macroscopic cerebral cortical formations and thence to neurological function. Using magnetic resonance imaging of the brain of the ferret, a model organism for studying cortical morphogenesis, we create in vitro physical gel models and in silico numerical simulations of normal brain gyrification. Using observations of genetically manipulated animal models, we identify cerebral cortical thickness and cortical expansion rate as the primary drivers of dysmorphogenesis and demonstrate that in silico models allow us to examine the causes of aberrations in morphology and developmental processes at various stages of cortical ontogenesis. Finally, we explain analogous cortical malformations in human brains, with comparisons with human phenotypes induced by the same genetic defects, providing a unified perspective on brain morphogenesis that is driven proximally by genetic causes and affected mechanically via variations in the geometry of the brain and differential growth of the cortex. Impact statementPhysical gel models and numerical simulations are created to study ferret brain gyrification and cortical malformations, and comparisons with human phenotypes are presented to link genetics and brain morphogenesis.

neuroscience↗

bioRxiv2025

Speed-accuracy trade-offs in Roulette betting

To investigate real-time decision-making in a simplified context, we analyze the trade-offs individuals make using a game of Roulette. In this game, players observe a ball that gradually decelerates as it moves around a circular track, and the participants must predict where the ball will ultimately stop. Players are rewarded for making rapid, accurate predictions, while slower but accurate predictions, or fast yet inaccurate ones, result in lower rewards. In this speed-accuracy trade-off setup we can calculate the optimal timing for placing a bet based on the balls initial speed and the deceleration rate, given the capacity of an individuals tracking abilities. We find that the participants improve their performance by accruing more reward with each trial and saturates close to the optimal performance, indicating that individuals learn the parameters of the physical model as well as a representation of the form of the reward under constrained time. Looking at the correlation between the bet time of the participant and the optimal betting time, the response delay and reward accrued, we find that the participant can be classified on a novice-expert spectrum. Our study offers ways to quantify human adaptation in competitive and dynamic environments such as sports, which may be helpful in enhancing participant performance.

animal behavior and cognition↗

bioRxiv2025

Convergent flow-mediated mesenchymal force drives embryonic foregut constriction and splitting

The transformation of a two-dimensional epithelial sheet into various three-dimensional structures is a critical process in generating the diversity of animal forms. Previous studies of epithelial folding have revealed diverse mechanisms driven by epithelium-intrinsic or -extrinsic forces. Yet little is known about the biomechanical basis of epithelial splitting, which involves extreme folding and eventually a topological transition breaking the epithelial tube. Here, we leverage tracheal-esophageal separation (TES), a critical and highly conserved morphogenetic event during tetrapod embryogenesis, as a model system for interrogating epithelial tube splitting both in vivo and ex vivo. Comparing TES in chick and mouse embryos, we identified an evolutionarily conserved, compressive force exerted by the mesenchyme surrounding the epithelium, as being necessary to drive epithelial constriction and splitting. The compressive force is mediated by localized convergent flow of mesenchymal cells towards the epithelium. We further found that Sonic hedgehog (SHH) secreted by the epithelium functions as an attractive cue for mesenchymal cells. Removal of the mesenchyme, inhibition of cell migration, or loss of SHH signaling all abrogate TES, which can be rescued by externally applied pressure. These results unveil the biomechanical basis of epithelial splitting and suggest plausible mesenchymal origins of tracheal-esophageal birth defects.

developmental biology↗

bioRxiv2024

Postural control in an upright snake

Posture and its control are fundamental aspects of animal behavior that capture the complex interplay between sensorimotor activity driven by muscular forces and mediated by environmental feedback. An extreme example of this is seen in brown tree snakes and juvenile pythons, which can stand almost upright, with 70% of their body length in the air. We quantify experimental observations of this behavior and present a minimal theoretical framework for postural stability by modeling the snake as an active elastic filament whose shape is controlled by muscular forces. We explore two approaches to characterize the musculature needed to achieve a specific posture: proprioceptive feedback (whereby the snake senses and reacts to its own shape) and a control-theoretic optimization approach (whereby the snake minimizes the expended energy to stand up), and also analyze the dynamic stability of the snake in its upright pose. Our results lead to a three-dimensional postural stability diagram in terms of muscle extent and strength, and gravity, consistent with experimental observations. In addition to general predictions about posture control in animals, our study suggests design principles for robotic mimics.

animal behavior and cognition↗

bioRxiv2024

Morphodynamics of tip growing cells

Pollen tubes, root hairs and fungal hyphae elongate by adding material at their tips. The region in the immediate vicinity of the tip is dynamically pliable and allows for the addition of new wall material even as it flows in response to the turgor that drives it. Any imbalance between the rate of material addition and its consequent flow will cause a tip growing cell to either burst because its wall thins or stop growing because its wall thickens. We use an experimentally-inspired feedback law that couples vesicle exocytosis to wall mechanics via the local strain rate to construct a minimal theory for the dynamics of tip growing cells. Our theory characterizes the parameter regime where stable steady tip growth is possible in terms of two dimensionless parameters: a scaled turgor pressure, and a ratio of length scales describing gradients of wall extensibility and vesicle composition near the tip. Our analysis also explains the experimentally observed shape response of tip growing cells observed when external turgor is dynamically varied. All together our formalism provides a general framework for the coupled dynamics of internal vesicular transport and wall mechanics in tip-growing cells.

plant biology↗

bioRxiv2024

Rules of departure: Antiphony and personalized vocal spaces in wild male elephant group coordination

In the intricate realm of animal communication, vocal signals play a vital role in maintaining bonds and coordinating group activities. Through detailed analysis of low-frequency rumble vocalizations of wild male African Savannah elephants, we demonstrate how these calls are employed in a coordinated manner. Our findings reveal a distinct pattern of call-and-response, usually initiated by a dominant male, with subsequent turn-taking responses from other group members. This antiphonal calling is instrumental in facilitating collective decision-making and group departures, highlighting a sophisticated level of communication previously unrecognized in male elephant groups. Furthermore, the study delves into the frequency content of these rumbles, finding significant individual variations in vocal characteristics. Analysis of the first two formant frequencies of these calls uncovers a distinct vocal space for each elephant, variable over time and across different social contexts. These individualized vocal spaces suggest a mechanism for personal identification within and across elephant groups, and may also relate to the information content of their vocal exchanges. The vocal spaces and structured antiphony presented in this study underline the complexity of elephant vocal communication and invite further targeted research into the vocal communication system of elephants, as well as inquiry into the cognitive and social aspects of wildlife communication in general.

animal behavior and cognition↗

bioRxiv2023

PEX1 is essential for the glycosome biogenesis and trypanosomatid parasite survival.

Trypanosomatid parasites are kinetoplastid protists that compartmentalize glycolytic enzymes in unique peroxisome-related organelles called glycosomes. The heterohexameric AAA-ATPase complex of PEX1-PEX6 is anchored to the peroxisomal membrane and functions in the export of matrix protein import receptor PEX5 from the peroxisomal membrane. Defects in PEX1, PEX6 or their membrane anchor causes dysfunction of peroxisomal matrix protein import cycle. In this study, we identified the Trypanosoma PEX1 orthologue using sequence and structural similarities. Using yeast two-hybrid analysis, we demonstrate that TbPEX1 can bind to TbPEX6. Endogenously tagged TbPEX1 localizes to glycosomes in the T. brucei parasites. Depletion of PEX1 gene expression by RNA interference causes lethality to bloodstream form trypanosomes, due to a partial mislocalization of glycosomal enzymes to the cytosol and ATP depletion. TbPEX1 RNAi leads to a selective proteasomal degradation of both matrix protein import receptors TbPEX5 and TbPEX7. Unlike in yeast, PEX1 depletion did not result in an accumulation of ubiquitinated TbPEX5 in trypanosomes. As PEX1 turned out to be essential for trypanosomatid parasites, it could provide a suitable drug target for parasitic diseases. The results also suggests that these parasites possess a highly efficient quality control mechanisms that export the import receptors from glycosomes to the cytosol, in the absence of a functional TbPEX1-TbPEX6 complex.

cell biology↗

bioRxiv2023

Hox genes modulate physical forces to differentially shape small and large intestinal epithelia

The small and large intestines arise from a common primordial gut tube but ultimately become specialized in both form and function. While the midgut forms villi, the hindgut develops flat, brain-like sulci that resolve into heterogeneous outgrowths. Gut compartment identities are demarcated early in development via Hox genes, which are highly conserved, master regulators of spatial patterning in the embryo. Yet, how these factors trigger regional morphogenesis has remained a mystery. Combining mechanical measurements and mathematical modeling, we demonstrate that the posterior Hox gene Hoxd13 regulates biophysical phenomena that shape the hindgut lumen. We further show that Hoxd13 acts through the TGF{beta} pathway to thicken, stiffen, and promote isotropic growth of the subepithelial mesenchyme; together, these features generate hindgut surface patterns. TGF{beta}, in turn, promotes collagen deposition to affect mesenchymal geometry and growth. We thus identify a cascade of events downstream of genetic identity that direct posterior intestinal morphogenesis.

developmental biology↗

bioRxiv2023

Beak morphometry and morphogenesis across avian radiations

Adaptive avian radiations associated with the diversification of bird beaks into a multitude of forms enabling different functions are exemplified by Darwins finches and Hawaiian honeycreepers. To elucidate the nature of these radiations, we quantified beak shape and skull shape using a variety of geometric measures that allowed us to collapse the variability of beak shape into a minimal set of geometric parameters. Furthermore, we find that just two measures of beak shape, the ratio of the width to length and the normalized sharpening rate (increase in the transverse beak curvature near the tip relative to that at the base of the beak), are both strongly correlated with diet, and thus indicative of how bite forces are correlated with beak shape. Finally, by considering how transverse sections to the beak centerline evolve with distance from the tip, we show that a simple geometry-driven growth law termed "modified mean curvature flow" captures the beak shapes of Darwins finches and Hawaiian honeycreepers. A surprising consequence of the simple growth law is that beak shapes that are not allowed based on the developmental program of the beak are also not observed in nature, suggesting a link between evolutionary morphology and development in terms of growth-driven developmental constraints.

evolutionary biology↗

bioRxiv2022

Activity-driven extracellular volume expansion drives vertebrate axis elongation

The vertebrate bauplan is primarily established via the formation of embryonic tissues in a head-to-tail progression. The biomechanics of this elongation, which requires the presomitic mesoderm (PSM), remains poorly understood. Here, we find that avian PSM explants can elongate autonomously when physically confined in vitro, producing a pushing force that can largely account for the posterior elongation of the embryo. Tissue elongation results from volumetric expansion that is driven by cellular activity and accompanied by inhomogeneous increase of the extracellular fraction along the AP axis. We show that FGF signaling promotes glycolysis-dependent production of Hyaluronic Acid (HA), which is required for expansion of the posterior PSM. Our findings link body axis elongation to tissue expansion through the metabolic control of extracellular matrix production downstream of FGF signaling. One-Sentence SummaryActive tissue expansion propels body elongation independent of cell proliferation-driven growth

developmental biology↗