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Biology subjects

Georgantzoglou, A.

Publications and source records attributed to Georgantzoglou, A..

3 recordsLinked to original sources

Chemotaxis of branched cells in complex environments

Cell migration in vivo is often guided by chemical signals. Such chemotaxis, such as performed by immune cells migrating to a wound site, is complicated by the complex geometry inside living tissues. In this study, we extend our theoretical model of branched-cell migration on a network by introducing chemokine sources to explore the cellular response. The model predicts a speed-accuracy tradeoff, whereby slow cells are significantly more accurate and able to follow efficiently a weak chemoattractant signal. We then compare the models predictions with experimental observations of neutrophils migrating to the site of laser-inflicted wound in a zebrafish larva fin, and migrating in-vitro inside a regular lattice of pillars. We find that the model captures the details of the sub-cellular response to the chemokine gradient, as well as the large-scale migration response. This comparison suggests that the neutrophils behave as fast cells, compromising their chemotaxis accuracy, which explains the functionality of these immune cells.

biophysics↗

Interstitial leukocyte navigation through a search and run response to gradients

Migrating cells must interpret chemical gradients to guide themselves within tissues. A general premise has been that gradients influence the direction of leading-edge protrusions. However, recent evidence indicates that actin flows correlate better with directed motion than protrusions. A unified chemotaxis model that integrates the role of protrusions and actin flows and that accounts for in vivo cell motion patterns is lacking. Here, we provide direct experimental evidence of how neutrophils sense gradients in real-time in vivo and demonstrate a two-stage process: first a search phase, that requires actin network expansion by Arp2/3, whereby cells slow down, explore the environment and execute path corrections. This is followed by a run phase, that requires Myosin-II-driven contractility and fast actin flows, whereby cells accelerate and persist in the source direction. Thus, protrusive forces support chemotaxis by enhancing signal detection, while actin flows act as the ultimate output of gradient processing.

cell biology↗

Neutrophil swarming in damaged tissue is orchestrated by connexin-dependent calcium signals

Neutrophils are major inflammatory cells that rapidly infiltrate injured tissues to provide antimicrobial functions. A key step in their response is the paracrine release of the attractant LTB4, which switches the migration mode from exploratory patrolling to coordinated swarming. This leads to dense clusters that may further disrupt tissue architecture. The coordination mechanism underpinning neutrophil swarms is elusive. Here we show that neutrophils swarms require mutual reinforcement of damage signalling at the wound core. New biosensors and live imaging in zebrafish revealed that neutrophil chemoattractant synthesis is triggered by a sustained calcium flux upon contact with necrotic tissue and sensing of the damage signal ATP. This calcium alarm signal propagates in the nascent neutrophil cluster through connexin-43 hemichannels, which allow release of intracellular ATP. This enables rapid assembly of a centralised, supracellular chemoattractant source, which is instrumental for coordinated recruitment and maximal cell gathering.

cell biology↗