Biology subjects

Alim, K.

Publications and source records attributed to Alim, K..

13 recordsLinked to original sources

bioRxiv2026

Distributed Network Sensing as an Escape Strategy

The response of a swarm of ants or birds, living tissue of cells, or a robotic swarm, to spatial signals from the environment as a whole is a fundamental challenge for these decentralized systems. A promising alternative is embodied distributed sensing and decision-making, so that local environmental cues directly shape coordinated reconfiguration, growth, or movement without centralized control. Fluidic networks offer a physical basis for such systems, yet existing implementations are predesigned and limited in their ability to process spatial information across extended systems. Here, we investigate how fluid transport networks enable environmental sensing and adaptive response using the slime mould Physarum polycephalum. By exposing Physarum vein networks to dynamic pH environments, we show that the organism's ability to respond to aversive stimuli is governed by its spatial extent and network connectivity. Above a certain size, organisms with network morphology reliably detect and escape harmful conditions by network reconfiguration, whereas disconnected or spatially confined organisms fail to respond. In environments with competing stimuli, network morphologies enable integration of spatial information and repositioning into favorable regions. We identify local contractions as a physical mechanism that drives fluid redistribution and converts local stimulation into system-level responses. Finally, we generate different morphologies using fluidic and electrochemical control, demonstrating large-scale adaptation to complex environments. These results establish distributed fluidic networks as a framework for integrated sensing and actuation, providing design principles for autonomous soft robotic systems in dynamic environments.

biophysics↗

bioRxiv2024

Flow-Induced Vascular Remodeling On-Chip: Implications for Anti-VEGF Therapy

Impaired vascular remodeling is linked to tumor progression, impacting the efficacy of anti-vascular therapies. However, the interplay between blood flow and vascular endothelial growth factor (VEGF) in driving vascular remodeling remains unclear. We optimized a human vasculature-on-chip system for long-term perfusion to quantify vascular remodeling under physiologically low and tumor-mimicking high VEGF conditions. Live imaging shows that at low VEGF levels, flow-conditioned vascular networks remodeled like animal models, en-hancing flow velocities. Conversely, static networks lacking flow exhibited continuous growth, loss of network hierarchy, and decreased flow velocities. At tumor-mimicking high VEGF levels, flow-conditioned vessels showed aberrant overgrowth, which was blocked by the anti-VEGF tumor drug bevacizumab, restoring flow-induced remodeling. Without flow, however, high VEGF slowed vessel growth compared to low VEGF, while anti-VEGF treatment restored continuous growth. These findings provide valuable insights into optimizing anti-angiogenic therapies by exploiting VEGF modulation and flow conditions for vascular remodeling and improved tumor treatment.

biophysics↗

bioRxiv2024

Mechanical forces instruct division plane orientation of cambium stem cells during radial growth in Arabidopsis thaliana

Precise regulation of cell division is central for the formation of complex multicellular organisms and a hallmark of stem cell activity. In plants, due to the absence of cell migration, correct placement of newly produced cell walls during cell division is of eminent importance for generating functional tissues and organs. In particular, during radial growth of plant shoots and roots, concerted cell divisions in the cambium are essential to produce adjacent xylem and phloem tissues in a strictly bidirectional manner. While several intercellular signaling cascades have been identified to instruct tissue organization during radial growth, a role of mechanical forces in guiding cambium stem cell activity has been frequently proposed but, so far, not been functionally investigated on the cellular level. Here, we coupled anatomical analyses with a cell-based vertex model to analyze the role of mechanical stress in radial plant growth at the cell and tissue scale. Simulations based on segmented cellular outlines of radially growing Arabidopsis hypocotyls revealed a distinct stress pattern with circumferential stresses in cambium stem cells which coincided with the orientation of cortical microtubules. Integrating stress patterns as a cue instructing cell division orientation was sufficient for the emergence of typical cambium-derived cell files and agreed with experimental results for stress-related tissue organization in confining mechanical environments. Our work thus underlines the significance of mechanical forces in tissue organization through self-emerging stress patterns during the growth of plant organs.

plant biology↗

bioRxiv2023

Mechanotransduction in Lateral Root Initiation: A Model Integrating Growth Mechanics and Auxin Signaling

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 post-embryonic 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 signalling 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 licence 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 signalling.

plant biology↗

bioRxiv2023

Vascular adaptation model from force balance: Physarum polycephalum as a case study

Understanding vascular adaptation, namely what drives veins to shrink or grow, is key for the self-organization of flow networks and their optimization. From the top-down principle of minimizing flow dissipation at a fixed metabolic cost within flow networks, flow shear rate resulting from the flows pervading veins is hypothesized to drive vein adaptation. Yet, there is no bottom-up derivation of how flow forces impact vein dynamics. From the physical principle of force balance, shear rate acts parallel to vein walls, and hence, naively shear rate could only stretch veins and not dilate or shrink them. We, here, resolve this paradox by theoretically investigating force balance on a vein wall in the context of the vascular network of the model organism P. polycephalum. We propose, based on previous mechanical studies of cross-linked gels, that shear induces a nonlinear, anisotropic response of the actomyosin gel, making up vein walls that can indeed drive vein dilatation. Furthermore, our force balance approach allows us to identify that shear feedback occurs with a typical timescale and with a typical target shear rate that are not universal properties of the material but instead depend smoothly on the location of the vein within the network. In particular, the target shear rate is related to the veins hydrostatic pressure, which highlights the role of pressure in vascular adaptation. Finally, since our derivation is based on force balance and fluid mechanics, we believe our approach can be extended to vascular adaptation in other organisms.

biophysics↗

bioRxiv2022

Network topology enables efficient response to environment in Physarum polycephalum

The network-shaped body plan distinguishes the unicellular slime mould Physarum polycephalum in 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 impacts P. polycephalums 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-shapeds 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.

biophysics↗

bioRxiv2022

Effective use of genetically-encoded optical biosensors for profiling signalling signatures in iPSC-CMs derived from idiopathic dilated cardiomyopathy patients

Dilated cardiomyopathy (DCM) is a cardiovascular condition that develops when the left ventricle of the heart enlarges, compromising its function and diminishing its capacity to pump oxygenated blood throughout the body. After patients are diagnosed with DCM, disease progression can lead to heart failure and the need for a heart transplantation. DCM is a complex disease where underlying causes can be idiopathic, genetic, or environmental. An incomplete molecular understanding of disease progression poses challenges for drug discovery efforts as effective therapeutics strategies remain elusive. Decades of research using primary cells or animal models have increased our understanding of DCM but has been hampered due to the inaccessibility of human cardiomyocytes, to model cardiac disease, in vitro, in a dish. Here, our goal is to leverage patient-derived hiPSC-CMs and to combine them with biosensors to understand how cellular signalling is altered in DCM. With high sensitivity and versatility, optical biosensors represent the ideal tools to dissect the molecular determinants of cardiovascular disease, in an unbiased manner and in real-time at the level of single cells. By characterizing the pathobiology of dilated cardiomyopathy in a patient-specific manner using high content biosensor-based assays, we aim to uncover personalized mechanisms for the occurrence and development of DCM and as a pathway to development of personalized therapeutics.

biochemistry↗

bioRxiv2022

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, independently 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.

biophysics↗

bioRxiv2021

Network architecture determines vein fate during spontaneous reorganization, with a time delay

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 veins 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 networks 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.

biophysics↗

bioRxiv2021

Nuclei are mobile processors enabling specialization 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 multinucleated 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-nucleated 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.

cell biology↗

bioRxiv2020

Emergence of behavior in a self-organized living matter network

What is the origin of behavior? Although typically associated with a nervous system, simple life forms also show complex behavior - thus serving as a model to study how behaviors emerge. Among them, the slime mold Physarum polycephalum, growing as a single giant cell, is renowned for its sophisticated behavior. Here, we show how locomotion and morphological adaptation behavior 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. Surprisingly, we find a continuous spectrum of modes, as opposed to few dominant modes. Over time, activation of modes along this continuous spectrum is highly dynamic, resulting in contraction patterns of varying regularity. We show that regular patterns are associated with stereotyped behavior by triggering a behavioral response with a food stimulus. Furthermore, we demonstrate that the continuous spectrum of modes and the existence of irregular contraction patterns persist in specimens with a morphology as simple as a single tube. Our data suggests that the continuous spectrum of modes allows for dynamic transitions between a plethora of specific behaviors with transitions marked by highly irregular contraction states. By mapping specific behaviors to states of active contractions, we provide the basis to understand behaviors complexity as a function of biomechanical dynamics. This perspective will likely stimulate bio-inspired design of soft robots with a similarly rich behavioral repertoire as P. polycephalum.

biophysics↗

bioRxiv2019

Tissue-wide integration of mechanical cues promotes efficient auxin patterning

New plants organs form by local accumulation of auxin, which is transported by PIN proteins that localize following mechanical stresses. As auxin itself modifies tissue mechanics, a feedback loop between tissue mechanics and auxin patterning unfolds - yet the impact of tissue-wide mechanical coupling on auxin pattern emergence remains unclear. Here, we use a hybrid model composed of a vertex model for plant tissue mechanics, and a compartment model for auxin transport to explore the collective mechanical response of the tissue to auxin patterns and how it feeds back onto auxin transport. We compare a model accounting for a tissue-wide mechanical integration to a model where mechanical stresses are averaged out across the tissue. We show that only tissue-wide mechanical coupling leads to focused auxin spots, which we show to result from the formation of a circumferential stress field around these spots, self-reinforcing PIN polarity and auxin accumulation.

plant biology↗

bioRxiv2019

An emergent flow of the nuclear array in syncytial embryos

Many aspects in tissue morphogenesis are attributed to the collective behavior of the participating cells. Yet, the mechanism for emergence of dynamic tissue behavior is not understood completely. Here we report the "yo-yo"-like nuclear drift movement in Drosophila syncytial embryo displays typical emergent feature of collective behavior, which is associated with pseudo-synchronous nuclear division cycle. We uncover the direct correlation between the degree of asynchrony of mitosis and the nuclear collective movement. Based on experimental manipulations and numerical simulations, we find the ensemble of spindle elongation, rather than a nucleus own spindle, is the main driving force for its drift movement. The cortical F-actin acts as viscoelastic medium to dampen the movements and plays a critical role in restoring the nuclear positions after a mitosis cycle. Our study provides insights into how the interactions between cytoskeleton as individual elements leads to collective movement of the nuclear array on a macroscopic scale.

developmental biology↗