Biology subjects

Mahadevan, L.

Publications and source records attributed to Mahadevan, L..

9 recordsLinked to original sources

bioRxiv2018

Filament extensibility and shear stiffening control persistence of strain and loss of coherence in cross-linked motor-filament assemblies

Cross-linked flexible filaments deformed by active molecular motors occur in many natural and synthetic settings including eukaryotic flagella, the cytoskeleton and in vitro motor assays. In these systems, an important quantity that controls spatial coordination and emergent collective behavior is the length scale over which elastic strains persist. We estimate this quantity in the context of ordered composites comprised of cross-linked elastic filaments sheared by active motors. Combining a mean-field theory valid for negligibly noisy systems with discrete simulations for noisy systems, we show that the effect of localized strains - be they steady or oscillatory - persist over distances determined by motor kinetics, motor elasticity and filament extensibility. The cut-off length that emerges from these effects controls the transmission of mechanical information and determines the criterion for spatially separated motor groups to stay synchronized. Our results generalize the notion of persistence in passive, Brownian filaments to active, cross-linked filaments.

biophysics↗

bioRxiv2018

Mechanical Coupling Coordinates the Co-elongation of Axial and Paraxial Tissues in Avian Embryos

Tissues undergoing morphogenesis impose mechanical effects on one another. How developmental programs adapt to or take advantage of these effects remains poorly explored. Here, using a combination of live imaging, modeling, and microsurgical perturbations, we show that the axial and paraxial tissues in the forming avian embryonic body coordinate their rates of elongation through mechanical interactions. First, a cell motility gradient drives paraxial presomitic mesoderm (PSM) expansion, resulting in compression of the axial neural tube and notochord; second, elongation of axial tissues driven by PSM compression and polarized cell intercalation pushes the caudal progenitor domain posteriorly; finally, the axial push drives progenitors to emigrate into the PSM to maintain tissue growth and cell motility. These interactions form an engine-like positive feedback loop, which ensures the tissue-coupling and self-sustaining characteristics of body elongation. Our results suggest a general role of inter-tissue forces in the coordination of complex morphogenesis involving distinct tissues.

developmental biology↗

bioRxiv2018

Hydraulic control of embryo size, tissue shape and cell fate

Size control is fundamental in tissue development and homeostasis1,2. While the role of cell proliferation in this process has been widely studied3, the mechanisms of organ size control and how it impacts cell fates remain elusive. Here, we use mouse blastocyst development as a model to unravel a key role of fluid-filled lumen in embryonic size control and cell fate specification. We find that during blastocyst expansion, there is a two-fold increase in the pressure of the lumen that translates into a concomitant increase in the cortical tension of trophectoderm (TE) cells lining the lumen. Increased cortical tension leads to vinculin mechanosensing and maturation of the functional tight junctions, thereby establishing a positive feedback loop to accommodate lumenal growth. However, when the cortical tension reaches a critical threshold, cell-cell adhesion cannot be sustained, and mitotic entry leads to a rupture of TE epithelium, fluid leakage and collapse of the blastocyst cavity. A simple theory of hydraulically-gated oscillations that integrates these feedback interactions recapitulates the evolution of cavity size and predicts the scaling of embryonic size with the tissue volume. Our theory further predicts that reduced cortical tension or disrupted tight junctions, and increased tissue stiffness lead to smaller embryonic size. These predictions are verified experimentally by embryological, pharmacological and genetic manipulations of the embryos. Remarkably, these changes to lumenal size, without a change in the tissue volume, lead to alteration of tissue architecture and cell fate. Overall, our study reveals how lumenal pressure and tissue mechanics control embryonic size at the tissue scale, that in turn couples to cell position and fate at the cellular scale.

developmental biology↗

bioRxiv2018

Size control of the inner ear via hydraulic feedback

Animals make organs of precise size, shape, and symmetry despite noise in underlying molecular and cellular processes. How developing organs manage this noise is largely unknown. Here, we combine quantitative imaging, physical theory, and physiological measurement of hydrostatic pressure and fluid transport in zebrafish to study size control of the developing inner ear. We find that fluid accumulation creates hydrostatic pressure in the lumen leading to stress in the epithelium and expansion of the otic vesicle. Pressure, in turn, inhibits fluid transport into the lumen. This negative feedback loop between pressure and transport allows the otic vesicle to change growth rate to control natural or experimentally-induced size variation. Spatiotemporal patterning of contractility modulates pressure-driven strain for regional tissue thinning. Our work connects moleculardriven mechanisms, such as osmotic pressure driven strain and actomyosin tension, to the regulation of tissue morphogenesis via hydraulic feedback to ensure robust control of organ size.

developmental biology↗

bioRxiv2018

Dynamics of spreading microbial swarms and films

Bacterial swarming and biofilm formation are collective multicellular phenomena through which diverse microbial species colonize and spread over water-permeable tissue. During both modes of surface translocation, fluid uptake and transport play a key role in shaping the overall morphology and spreading dynamics. Here, using Bacillus subtilis as our model experimental system, we develop a generalized two-phase thin-film model that couples hydrodynamics, mechanics, osmotic flux and nutrient transport to describe the expansion of both highly motile bacterial swarms, and sessile bacterial biofilms. We show that swarm expansion corresponds to steady-state solutions in a nutrient-rich, capillarity dominated regime. In contrast, biofilm colony growth is described by transient solutions associated with a nutrient-limited, extracellular polymer stress driven limit. We apply our unified framework to explain a range of recent experimental observations associated with the shape, form and dynamics of Escherichia coli and Bacillus subtilis swarms and biofilms. Our results demonstrate how hydrodynamics and transport serve as key physical constraints in regulating biological organization and function in microbial communities.

biophysics↗

bioRxiv2017

Fluid mediated self-organization of ventilation in honeybee nests

European honey bees (Apis mellifera) live in large congested nest cavities with a single opening that limits passive ventilation. These nests are actively ventilated by individual bees which fan their wings at the nest entrance when the local air temperature exceeds a threshold. Here we show that colonies with relatively large nest entrances use an emergent ventilation strategy where fanning bees self-organize to form fanning groups, separating regions of continuous inflow and outflow. The observed spatio-temporal patterns correlate the air velocity and air temperature along the entrances to the distribution of fanning bees. A mathematical model that couples these variables to known fanning behavior of individuals recapitulates their collective dynamics. Additionally, the model makes predictions about the temporal stability of the fanning group as a function of the temperature difference between the environment and the nest. Consistent with these predictions, we observe that the fanning groups drift, cling to the entrance boundaries, break-up and reform as the ambient temperature varies over a period of days. Overall, our study shows how honeybees use flow-mediated communication to self-organize into a steady-state in fluctuating environments.

animal behavior and cognition↗

bioRxiv2017

Collective mechanical adaptation of honeybee swarms

Honeybee Apis mellifera swarms form clusters made solely of bees attached to each other, forming pendant structures on tree branches (1). These clusters can be hundreds of times the size of a single organism. How these structures are stably maintained under the influence of static gravity and dynamic stimuli (e.g. wind) is unknown. To address this, we created pendant conical clusters attached to a board that was shaken with varying amplitude, frequency and total duration. Our observations show that horizontally shaken clusters spread out to form wider, flatter cones, i.e. the cluster adapts to the dynamic loading conditions, but in a reversible manner - when the loading is removed, the cluster recovers its original shape, slowly. Measuring the response of a cluster to a sharp pendular excitation before and after it adapted shows that the flattened cones deform less and relax faster than the elongated ones, i.e. they are more stable mechanically. We use particle-based simulations of a passive assemblage to suggest a behavioral hypothesis that individual bees respond to local variations in strain. This behavioral response improves the collective stability of the cluster as a whole at the expense of increasing the average mechanical burden experienced by the individual. Simulations using this rule explain our observations of adaptation to horizontal shaking. The simulations also suggest that vertical shaking will not lead to significant differential strains and thus no adaptation. To test this, we shake the cluster vertically and find that indeed there is no response to this stimulus. Altogether, our results show how an active, functional super-organism structure can respond adaptively to dynamic mechanical loading by changing its morphology to achieve better load sharing.

animal behavior and cognition↗

bioRxiv2017

Motility-gradient induced elongation of the vertebrate embryo

The body of vertebrate embryos forms by posterior elongation from a terminal growth zone called the Tail Bud (TB). The TB produces highly motile cells forming the presomitic mesoderm (PSM), a tissue playing an important role in elongation movements. PSM cells establish an anterior-posterior cell motility gradient which parallels the degradation of a specific cellular signal (Fgf8) known to be implicated in cell motility. Here, we combine electroporation of fluorescent reporters in the PSM to time-lapse imaging in the chicken embryo to quantify cell diffusive movements along the motility gradient. We show that simple microscopic and macroscopic mechano-chemical models for tissue extension that couple Fgf activity, cell motility and tissue rheology at both the cellular and continuum levels suffice to capture the speed and extent of elongation. These observations explain how the continuous addition of cells that exhibit a gradual reduction in motility combined with lateral confinement can be converted into an oriented movement that drives body elongation. The results of the models compare well with our experimental results, with implications for other elongation processes in the embryo.

developmental biology↗

bioRxiv2017

The statistical nature of geometric reasoning

Geometric reasoning has an inherent dissonance: its abstract axioms and propositions refer to infinitesimal points and infinite straight lines while our perception of the physical world deals with fuzzy dots and curved stripes. How we use these disparate mechanisms to make geometric judgments remains unresolved. Here, we deploy a classically used cognitive geometric task - planar triangle completion - to study the statistics of errors in the location of the missing vertex. Our results show that the mean location has an error proportional to the side of the triangle, the standard deviation is sub-linearly dependent on the side length, and has a negative skewness. These scale-dependent responses directly contradict the conclusions of recent cognitive studies that innate Euclidean rules drive our geometric judgments. To explain our observations, we turn to a perceptual basis for geometric reasoning that balances the competing effects of local smoothness and global orientation of extrapolated trajectories. The resulting mathematical framework captures our observations and further predicts the statistics of the missing angle in a second triangle completion task. To go beyond purely perceptual geometric tasks, we carry out a categorical version of triangle completion that asks about the change in the missing angle after a change in triangle shape. The observed responses show a systematic scale-dependent discrepancy at odds with rule-based Euclidean reasoning, but one that is completely consistent with our framework. All together, our findings point to the use of statistical dynamic models of the noisy perceived physical world, rather than on the abstract rules of Euclid in determining how we reason geometrically.

animal behavior and cognition↗