7 research outputs found
Boundary-interior principle for microbial navigation in geometric confinement
When the motion of a motile cell is observed closely, it appears erratic, and
yet the combination of nonequilibrium forces and surfaces can produce striking
examples of collective organization in microbial systems. While our current
understanding is based on bulk systems or idealized geometries, it is not clear
at which length scale self-organization emerges. Here, using experiments,
analytical and numerical calculations we study the motion of motile cells under
controlled microfluidic conditions, and demonstrate that a robust topology of
probability flux loops organizes active motion even at the level of a single
cell exploring an isolated habitat. By accounting for the interplay of activity
and interfacial forces, we find that the boundary's curvature determines the
nonequilibrium probability fluxes of the motion, which can be controlled
directly. We theoretically predict a universal relation between fluxes and
global geometric properties that is directly confirmed by experiments. Our
findings open the possibility to decipher the most probable trajectories of
motile cells and may enable the design of active topological materials
Neural mechanisms of parasite-induced summiting behavior in âzombieâ Drosophila
For at least two centuries, scientists have been enthralled by the âzombieâ behaviors induced by mind-controlling parasites. Despite this interest, the mechanistic bases of these uncanny processes have remained mostly a mystery. Here, we leverage the Entomophthora muscae-Drosophila melanogaster âzombie flyâ system to reveal the mechanistic underpinnings of summit disease, a manipulated behavior evoked by many fungal parasites. Using a high-throughput approach to measure summiting, we discovered that summiting behavior is characterized by a burst of locomotion and requires the host circadian and neurosecretory systems, specifically DN1p circadian neurons, pars intercerebralis to corpora allata projecting (PI-CA) neurons and corpora allata (CA), the latter being solely responsible for juvenile hormone (JH) synthesis and release. Using a machine learning classifier to identify summiting animals in real time, we observed that PI-CA neurons and CA appeared intact in summiting animals, despite invasion of adjacent regions of the âzombie flyâ brain by E. muscae cells and extensive host tissue damage in the body cavity. The blood-brain barrier of flies late in their infection was significantly permeabilized, suggesting that factors in the hemolymph may have greater access to the central nervous system during summiting. Metabolomic analysis of hemolymph from summiting flies revealed differential abundance of several compounds compared to non-summiting flies. Transfusing the hemolymph of summiting flies into non-summiting recipients induced a burst of locomotion, demonstrating that factor(s) in the hemolymph likely cause summiting behavior. Altogether, our work reveals a neuro-mechanistic model for summiting wherein fungal cells perturb the flyâs hemolymph, activating a neurohormonal pathway linking clock neurons to juvenile hormone production in the CA, ultimately inducing locomotor activity in their host
Emergent probability fluxes in confined microbial navigation
When the motion of a motile cell is observed closely, it appears erratic, and yet the combination of nonequilibrium forces and surfaces can produce striking examples of organization in microbial systems. While most of our current understanding is based on bulk systems or idealized geometries, it remains elusive how and at which length scale self-organization emerges in complex geometries. Here, using experiments and analytical and numerical calculations, we study the motion of motile cells under controlled microfluidic conditions and demonstrate that probability flux loops organize active motion, even at the level of a single cell exploring an isolated compartment of nontrivial geometry. By accounting for the interplay of activity and interfacial forces, we find that the boundaryâs curvature determines the nonequilibrium probability fluxes of the motion. We theoretically predict a universal relation between fluxes and global geometric properties that is directly confirmed by experiments. Our findings open the possibility to decipher the most probable trajectories of motile cells and may enable the design of geometries guiding their time-averaged motion
Emergent probability fluxes in confined microbial navigation: Data and code
Data and code to go alongside the publication of:"Emergent probability fluxes in confined microbial navigation"</div
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Bayesian modeling reveals metabolite-dependent ultrasensitivity in the cyanobacterial circadian clock.
Mathematical models can enable a predictive understanding of mechanism in cell biology by quantitatively describing complex networks of interactions, but such models are often poorly constrained by available data. Owing to its relative biochemical simplicity, the core circadian oscillator in Synechococcus elongatus has become a prototypical system for studying how collective dynamics emerge from molecular interactions. The oscillator consists of only three proteins, KaiA, KaiB, and KaiC, and near-24-h cycles of KaiC phosphorylation can be reconstituted in vitro. Here, we formulate a molecularly detailed but mechanistically naive model of the KaiA-KaiC subsystem and fit it directly to experimental data within a Bayesian parameter estimation framework. Analysis of the fits consistently reveals an ultrasensitive response for KaiC phosphorylation as a function of KaiA concentration, which we confirm experimentally. This ultrasensitivity primarily results from the differential affinity of KaiA for competing nucleotide-bound states of KaiC. We argue that the ultrasensitive stimulus-response relation likely plays an important role in metabolic compensation by suppressing premature phosphorylation at nighttime
Bayesian modeling reveals metaboliteâdependent ultrasensitivity in the cyanobacterial circadian clock
Abstract Mathematical models can enable a predictive understanding of mechanism in cell biology by quantitatively describing complex networks of interactions, but such models are often poorly constrained by available data. Owing to its relative biochemical simplicity, the core circadian oscillator in Synechococcus elongatus has become a prototypical system for studying how collective dynamics emerge from molecular interactions. The oscillator consists of only three proteins, KaiA, KaiB, and KaiC, and nearâ24âh cycles of KaiC phosphorylation can be reconstituted in vitro. Here, we formulate a molecularly detailed but mechanistically naive model of the KaiAâKaiC subsystem and fit it directly to experimental data within a Bayesian parameter estimation framework. Analysis of the fits consistently reveals an ultrasensitive response for KaiC phosphorylation as a function of KaiA concentration, which we confirm experimentally. This ultrasensitivity primarily results from the differential affinity of KaiA for competing nucleotideâbound states of KaiC. We argue that the ultrasensitive stimulusâresponse relation likely plays an important role in metabolic compensation by suppressing premature phosphorylation at nighttime
Bayesian modeling reveals metaboliteâdependent ultrasensitivity in the cyanobacterial circadian clock
Abstract Mathematical models can enable a predictive understanding of mechanism in cell biology by quantitatively describing complex networks of interactions, but such models are often poorly constrained by available data. Owing to its relative biochemical simplicity, the core circadian oscillator in Synechococcus elongatus has become a prototypical system for studying how collective dynamics emerge from molecular interactions. The oscillator consists of only three proteins, KaiA, KaiB, and KaiC, and nearâ24âh cycles of KaiC phosphorylation can be reconstituted in vitro. Here, we formulate a molecularly detailed but mechanistically naive model of the KaiAâKaiC subsystem and fit it directly to experimental data within a Bayesian parameter estimation framework. Analysis of the fits consistently reveals an ultrasensitive response for KaiC phosphorylation as a function of KaiA concentration, which we confirm experimentally. This ultrasensitivity primarily results from the differential affinity of KaiA for competing nucleotideâbound states of KaiC. We argue that the ultrasensitive stimulusâresponse relation likely plays an important role in metabolic compensation by suppressing premature phosphorylation at nighttime