Auxin-mediated stress relaxation in pericycle and endoderm remodeling drives lateral root initiation.

Plant development relies on the precise coordination of cell growth, which is influenced by the mechanical constraints imposed by rigid cell walls. The hormone auxin plays a crucial role in regulating this growth by altering the mechanical properties of cell walls. During the postembryonic formation of lateral roots, pericycle cells deep within the main root are triggered by auxin to resume growth and divide to form a new root. This growth involves a complex interplay between auxin, growth, and the resolution of mechanical conflicts with the overlying endodermis. However, the exact mechanisms by which this coordination is achieved are still unknown. Here, we propose a model that integrates tissue mechanics and auxin transport, revealing a connection between the auxin-induced relaxation of mechanical stress in the pericycle and auxin signaling in the endodermis. We show that the endodermis initially limits the growth of pericycle cells, resulting in a modest initial expansion. However, the associated stress relaxation is sufficient to redirect auxin to the overlying endodermis, which then actively accommodates the growth, allowing for the subsequent development of the lateral root. Our model uncovers that increased pericycle turgor and decreased endodermal resistance license expansion of the pericycle and how the topology of the endodermis influences the formation of the new root. These findings highlight the interconnected relationship between mechanics and auxin flow during lateral root initiation, emphasizing the vital role of the endodermis in shaping root development through mechanotransduction and auxin signaling.

Size-dependent self-avoidance enables superdiffusive migration in macroscopic unicellulars.

Many cells face search problems, such as finding food, mates, or shelter, where their success depends on their search strategy. In contrast to other unicellular organisms, the slime mold Physarum polycephalum forms a giant network-shaped plasmodium while foraging for food. What is the advantage of the giant cell on the verge of multicellularity? We experimentally study and quantify the migration behavior of P. polycephalum plasmodia on the time scale of days in the absence and presence of food. We develop a model which successfully describes its migration in terms of ten data-derived parameters. Using the mechanistic insights provided by our data-driven model, we find that regardless of the absence or presence of food, P. polycephalum achieves superdiffusive migration by performing a self-avoiding run-and-tumble movement. In the presence of food, the run duration statistics change, only controlling the short-term migration dynamics. However, varying organism size, we find that the long-term superdiffusion arises from self-avoidance determined by cell size, highlighting the potential evolutionary advantage that this macroscopically large cell may have.

Calcium regulates cortex contraction inPhysarum polycephalum.

The tubular network-forming slime moldPhysarum polycephalumis able to maintain long-scale contraction patterns driven by an actomyosin cortex. The resulting shuttle streaming in the network is crucial for the organism to respond to external stimuli and reorganize its body mass giving rise to complex behaviors. However, the chemical basis of the self-organized flow pattern is not fully understood. Here, we present ratiometric measurements of free intracellular calcium in simple morphologies ofPhysarumnetworks. The spatiotemporal patterns of the free calcium concentration reveal a nearly anti-correlated relation to the tube radius, suggesting that calcium is indeed a key regulator of the actomyosin activity. We compare the experimentally observed phase relation between the radius and the calcium concentration to the predictions of a theoretical model including calcium as an inhibitor. Numerical simulations of the model suggest that calcium indeed inhibits the contractions inPhysarum, although a quantitative difference to the experimentally measured phase relation remains. Unraveling the mechanism underlying the contraction patterns is a key step in gaining further insight into the principles ofPhysarum's complex behavior.

Alkaline vents recreated in two dimensions to study pH gradients, precipitation morphology, and molecule accumulation.

Alkaline vents (AVs) are hypothesized to have been a setting for the emergence of life, by creating strong gradients across inorganic membranes within chimney structures. In the past, three-dimensional chimney structures were formed under laboratory conditions; however, no in situ visualization or testing of the gradients was possible. We develop a quasi-two-dimensional microfluidic model of AVs that allows spatiotemporal visualization of mineral precipitation in low-volume experiments. Upon injection of an alkaline fluid into an acidic, iron-rich solution, we observe a diverse set of precipitation morphologies, mainly controlled by flow rate and ion concentration. Using microscope imaging and pH-dependent dyes, we show that finger-like precipitates can facilitate formation and maintenance of microscale pH gradients and accumulation of dispersed particles in confined geometries. Our findings establish a model to investigate the potential of gradients across a semipermeable boundary for early compartmentalization, accumulation, and chemical reactions at the origins of life.

Flow-driven control of pulse width in excitable media.

Models of pulse formation in nerve conduction have provided manifold insight not only into neuronal dynamics but also the nonlinear dynamics of pulse formation in general. Recent observation of neuronal electrochemical pulses also driving mechanical deformation of the tubular neuronal wall, and thereby generating ensuing cytoplasmic flow, now question the impact of flow on the electrochemical dynamics of pulse formation. Here, we theoretically investigate the classical Fitzhugh-Nagumo model, now accounting for advective coupling between the pulse propagator typically describing membrane potential and triggering mechanical deformations, and thus governing flow magnitude, and the pulse controller, a chemical species advected with the ensuing fluid flow. Employing analytical calculations and numerical simulations, we find that advective coupling allows for a linear control of pulse width while leaving pulse velocity unchanged. We therefore uncover an independent control of pulse width by fluid flow coupling.

Network topology enables efficient response to environment inPhysarum polycephalum.

The network-shaped body plan distinguishes the unicellular slime mouldPhysarum polycephalumin body architecture from other unicellular organisms. Yet, network-shaped body plans dominate branches of multi-cellular life such as in fungi. What survival advantage does a network structure provide when facing a dynamic environment with adverse conditions? Here, we probe how network topology impactsP. polycephalum's avoidance response to an adverse blue light. We stimulate either an elongated, I-shaped amoeboid or a Y-shaped networked specimen and subsequently quantify the evacuation process of the light-exposed body part. The result shows that Y-shaped specimen complete the avoidance retraction in a comparable time frame, even slightly faster than I-shaped organisms, yet, at a lower almost negligible increase in migration velocity. Contraction amplitude driving mass motion is further only locally increased in Y-shaped specimen compared to I-shaped-providing further evidence that Y-shaped's avoidance reaction is energetically more efficient than in I-shaped amoeboid organisms. The difference in the retraction behaviour suggests that the complexity of network topology provides a key advantage when encountering adverse environments. Our findings could lead to a better understanding of the transition from unicellular to multicellularity.

Memory capacity of adaptive flow networks.

Biological flow networks adapt their network morphology to optimize flow while being exposed to external stimuli from different spatial locations in their environment. These adaptive flow networks retain a memory of the stimulus location in the network morphology. Yet, what limits this memory and how many stimuli can be stored are unknown. Here, we study a numerical model of adaptive flow networks by applying multiple stimuli subsequently. We find strong memory signals for stimuli imprinted for a long time into young networks. Consequently, networks can store many stimuli for intermediate stimulus duration, which balance imprinting and aging.

Vein fate determined by flow-based but time-delayed integration of network architecture.

Veins in vascular networks, such as in blood vasculature or leaf networks, continuously reorganize, grow or shrink, to minimize energy dissipation. Flow shear stress on vein walls has been set forth as the local driver for a vein's continuous adaptation. Yet, shear feedback alone cannot account for the observed diversity of vein dynamics - a puzzle made harder by scarce spatiotemporal data. Here, we resolve network-wide vein dynamics and shear rate during spontaneous reorganization in the prototypical vascular networks of Physarum polycephalum. Our experiments reveal a plethora of vein dynamics (stable, growing, shrinking) where the role of shear is ambiguous. Quantitative analysis of our data reveals that (a) shear rate indeed feeds back on vein radius, yet, with a time delay of 1-3 min. Further, we reconcile the experimentally observed disparate vein fates by developing a model for vein adaptation within a network and accounting for the observed time delay. The model reveals that (b) vein fate is determined by parameters - local pressure or relative vein resistance - which integrate the entire network's architecture, as they result from global conservation of fluid volume. Finally, we observe avalanches of network reorganization events that cause entire clusters of veins to vanish. Such avalanches are consistent with network architecture integrating parameters governing vein fate as vein connections continuously change. As the network architecture integrating parameters intrinsically arise from laminar fluid flow in veins, we expect our findings to play a role across flow-based vascular networks.

Dispersive transport dynamics in porous media emerge from local correlations.

Understanding and controlling transport through complex media is central for a plethora of processes ranging from technical to biological applications. Yet, the effect of micro-scale manipulations on macroscopic transport dynamics still poses conceptual conundrums. Here, we demonstrate the predictive power of a conceptual shift in describing complex media by local micro-scale correlations instead of an assembly of uncorrelated minimal units. Specifically, we show that the non-linear dependency between microscopic morphological properties and macroscopic transport characteristics in porous media is captured by transport statistics on the level of pore junctions instead of single pores. Probing experimentally and numerically transport through two-dimensional porous media while gradually increasing flow heterogeneity, we find a non-monotonic change in transport efficiency. Using analytic arguments, we built physical intuition on how this non-monotonic dependency emerges from junction statistics. The shift in paradigm presented here broadly affects our understanding of transport within the diversity of complex media.

Changing Flows Balance Nutrient Absorption and Bacterial Growth along the Gut.

Small intestine motility and its ensuing flow of luminal content impact both nutrient absorption and bacterial growth. To explore this interdependence we introduce a biophysical description of intestinal flow and absorption. Rooted in observations of mice we identify the average flow velocity as the key control of absorption efficiency and bacterial growth, independent of the exact contraction pattern. We uncover self-regulation of contraction and flow in response to nutrients and bacterial levels to promote efficient absorption while restraining detrimental bacterial overgrowth.

Memory Formation in Adaptive Networks.

The continuous adaptation of networks like our vasculature ensures optimal network performance when challenged with changing loads. Here, we show that adaptation dynamics allow a network to memorize the position of an applied load within its network morphology. We identify that the irreversible dynamics of vanishing network links encode memory. Our analytical theory successfully predicts the role of all system parameters during memory formation, including parameter values which prevent memory formation. We thus provide analytical insight on the theory of memory formation in disordered systems.

Spatial transcriptomic and single-nucleus analysis reveals heterogeneity in a gigantic single-celled syncytium.

In multicellular organisms, the specification, coordination, and compartmentalization of cell types enable the formation of complex body plans. However, some eukaryotic protists such as slime molds generate diverse and complex structures while remaining in a multinucleate syncytial state. It is unknown if different regions of these giant syncytial cells have distinct transcriptional responses to environmental encounters and if nuclei within the cell diversify into heterogeneous states. Here, we performed spatial transcriptome analysis of the slime mold Physarum polycephalum in the plasmodium state under different environmental conditions and used single-nucleus RNA-sequencing to dissect gene expression heterogeneity among nuclei. Our data identifies transcriptome regionality in the organism that associates with proliferation, syncytial substructures, and localized environmental conditions. Further, we find that nuclei are heterogenous in their transcriptional profile and may process local signals within the plasmodium to coordinate cell growth, metabolism, and reproduction. To understand how nuclei variation within the syncytium compares to heterogeneity in single-nucleus cells, we analyzed states in single Physarum amoebal cells. We observed amoebal cell states at different stages of mitosis and meiosis, and identified cytokinetic features that are specific to nuclei divisions within the syncytium. Notably, we do not find evidence for predefined transcriptomic states in the amoebae that are observed in the syncytium. Our data shows that a single-celled slime mold can control its gene expression in a region-specific manner while lacking cellular compartmentalization and suggests that nuclei are mobile processors facilitating local specialized functions. More broadly, slime molds offer the extraordinary opportunity to explore how organisms can evolve regulatory mechanisms to divide labor, specialize, balance competition with cooperation, and perform other foundational principles that govern the logic of life.

Emergence of behaviour in a self-organized living matter network.

What is the origin of behaviour? Although typically associated with a nervous system, simple organisms also show complex behaviours. Among them, the slime mold Physarum polycephalum, a giant single cell, is ideally suited to study emergence of behaviour. Here, we show how locomotion and morphological adaptation behaviour emerge from self-organized patterns of rhythmic contractions of the actomyosin lining of the tubes making up the network-shaped organism. We quantify the spatio-temporal contraction dynamics by decomposing experimentally recorded contraction patterns into spatial contraction modes. Notably, we find a continuous spectrum of modes, as opposed to a few dominant modes. Our data suggests that the continuous spectrum of modes allows for dynamic transitions between a plethora of specific behaviours with transitions marked by highly irregular contraction states. By mapping specific behaviours to states of active contractions, we provide the basis to understand behaviour's complexity as a function of biomechanical dynamics.

Gut microbiota-motility interregulation: insights from in vivo, ex vivo and in silico studies.

The human gastrointestinal tract is home to trillions of microbes. Gut microbial communities have a significant regulatory role in the intestinal physiology, such as gut motility. Microbial effect on gut motility is often evoked by bioactive molecules from various sources, including microbial break down of carbohydrates, fibers or proteins. In turn, gut motility regulates the colonization within the microbial ecosystem. However, the underlying mechanisms of such regulation remain obscure. Deciphering the inter-regulatory mechanisms of the microbiota and bowel function is crucial for the prevention and treatment of gut dysmotility, a comorbidity associated with many diseases. In this review, we present an overview of the current knowledge on the impact of gut microbiota and its products on bowel motility. We discuss the currently available techniques employed to assess the changes in the intestinal motility. Further, we highlight the open challenges, and incorporate biophysical elements of microbes-motility interplay, in an attempt to lay the foundation for describing long-term impacts of microbial metabolite-induced changes in gut motility.

Encoding memory in tube diameter hierarchy of living flow network.

The concept of memory is traditionally associated with organisms possessing a nervous system. However, even very simple organisms store information about past experiences to thrive in a complex environment-successfully exploiting nutrient sources, avoiding danger, and warding off predators. How can simple organisms encode information about their environment? We here follow how the giant unicellular slime mold Physarum polycephalum responds to a nutrient source. We find that the network-like body plan of the organism itself serves to encode the location of a nutrient source. The organism entirely consists of interlaced tubes of varying diameters. Now, we observe that these tubes grow and shrink in diameter in response to a nutrient source, thereby imprinting the nutrient's location in the tube diameter hierarchy. Combining theoretical model and experimental data, we reveal how memory is encoded: a nutrient source locally releases a softening agent that gets transported by the cytoplasmic flows within the tubular network. Tubes receiving a lot of softening agent grow in diameter at the expense of other tubes shrinking. Thereby, the tubes' capacities for flow-based transport get permanently upgraded toward the nutrient location, redirecting future decisions and migration. This demonstrates that nutrient location is stored in and retrieved from the networks' tube diameter hierarchy. Our findings explain how network-forming organisms like slime molds and fungi thrive in complex environments. We here identify a flow networks' version of associative memory-very likely of relevance for the plethora of living flow networks as well as for bioinspired design.

The Emergent Yo-yo Movement of Nuclei Driven by Cytoskeletal Remodeling in Pseudo-synchronous Mitotic Cycles.

Many aspects in tissue morphogenesis are attributed to a collective behavior of the participating cells. Yet, the mechanism for emergence of dynamic tissue behavior is not well understood. Here, we report that the "yo-yo"-like nuclear movement in the Drosophila syncytial embryo displays emergent features indicative of collective behavior. Following mitosis, the array of nuclei moves away from the wave front by several nuclear diameters only to return to its starting position about 5 min later. Based on experimental manipulations and numerical simulations, we find that the ensemble of elongating and isotropically oriented spindles, rather than individual spindles, is the main driving force for anisotropic nuclear movement. ELMO-dependent F-actin restricts the time for the forward movement and ELMO- and dia-dependent F-actin is essential for the return movement. Our study provides insights into how the interactions among the cytoskeleton as individual elements lead to collective movement of the nuclear array on a macroscopic scale.

Living System Adapts Harmonics of Peristaltic Wave for Cost-Efficient Optimization of Pumping Performance.

Wavelike patterns driving transport are ubiquitous in life. Peristaltic pumps are a paradigm of efficient mass transport by contraction driven flows-often limited by energetic constraints. We show that a cost-efficient increase in pumping performance can be achieved by modulating the phase difference between harmonics to increase occlusion. In experiments we find a phase difference shift in the living peristalsis model P. polycephalum as dynamic response to forced mass transport. Our findings provide a novel metric for wavelike patterns and demonstrate the crucial role of nonlinearities in life.

Robust Increase in Supply by Vessel Dilation in Globally Coupled Microvasculature.

Neuronal activity induces changes in blood flow by locally dilating vessels in the brain microvasculature. How can the local dilation of a single vessel increase flow-based metabolite supply, given that flows are globally coupled within microvasculature? Solving the supply dynamics for rat brain microvasculature, we find one parameter regime to dominate physiologically. This regime allows for robust increase in supply independent of the position in the network, which we explain analytically. We show that local coupling of vessels promotes spatially correlated increased supply by dilation.

Feedback from Tissue Mechanics Self-Organizes Efficient Outgrowth of Plant Organ.

Plant organ outgrowth superficially appears like the continuous mechanical deformation of a sheet of cells. Yet, how precisely cells as individual mechanical entities can act to morph a tissue reliably and efficiently into three dimensions during outgrowth is still puzzling, especially when cells are tightly connected as in plant tissue. In plants, the mechanics of cells within a tissue is particularly well-defined because individual cell growth is essentially the mechanical yielding of the cell wall in response to internal turgor pressure. Cell-wall stiffness is controlled by biological signaling, which is impacted by stresses, and hence, cell growth is observed to respond to mechanical stresses building up within a tissue. What is the role of the mechanical feedback during morphing of tissue in three dimensions? Here, we develop a three-dimensional vertex model to investigate tissue mechanics at the onset of organ outgrowth at the tip of a plant shoot. We find that organ height is primarily governed by the ratio of growth rates of faster-growing cells initiating the organ versus slower-growing cells surrounding them. Remarkably, the outgrowth rate is higher when cell growth responds to the tissue-wide mechanical stresses. Our quantitative analysis of simulation data shows that tissue mechanical feedback on cell growth can act via a twofold mechanism. First, the feedback guides patterns of cellular growth. Second, the feedback modifies the stress patterns on the cells, consequently amplifying and propagating growth anisotropies. This mechanism may allow plants to grow organs efficiently out of the meristem by reorganizing the cellular growth rather than inflating growth rates.