Nir Gov's Lab

Cell migration in vivo is often guided by chemical signaling, i.e., chemotaxis. For immune cells performing chemotaxis in the organism, this process is influenced by the complex geometry of the tissue environment. In this study, we use a theoretical model of branched cell migration on a network to explore the cellular response to chemical gradients. The model predicts the response of a branched cell to a chemical gradient: how the cell reorients its internal polarity and how it navigates through a complex environment up a chemical gradient. We then compare the model's predictions with experimental observations of neutrophils migrating to the site of a laser-inflicted wound in a zebrafish larva fin, and neutrophils migrating in vitro inside a regular lattice of pillars. We find that the model captures the details of the subcellular response to the chemokine gradient, as well as qualitative characteristics of the large-scale migration, suggesting that the neutrophils behave as fast cells, which explains the functionality of these immune cells.

Motile cells often face microenvironmental constraints and obstacles that force them to extend multiple protrusions. However, the analysis of shape dynamics during directional decision-making has been restricted to single junctions. Here, we combined live-cell imaging and a coarse-grained model to study the migratory behavior of highly branched cells while simultaneously facing several junctions. The theoretical model predicts that the choice of a new direction is determined by the competition between the cellular protrusions in the form of seesaw oscillations. We found that macrophages and endothelial cells display different regimes moving on hexagonal networks, despite sharing a mesenchymal (i.e., adhesion-dependent) migratory strategy. The model describes the motility of both cell types and reveals a trade-off between branching and speed: Having many protrusions allows local microenvironmental exploration for directional cues, but long-range migration efficiency improves with fewer protrusions. Collectively, our data highlight the relevance and provide insights for the regulation of shape dynamics during cell navigation in complex geometries.

We study how simple eukaryotic organisms make decisions in response to competing stimuli in the context of phototaxis by the unicellular alga Chlamydomonas reinhardtii. While negatively phototactic cells swim directly away from a collimated light beam, when presented with two beams of adjustable intersection angle and intensities, we find that cells swim in a direction given by an intensity-weighted average of the two light propagation vectors. This geometrical law is a fixed point of an adaptive model of phototaxis and minimizes the average light intensity falling on the anterior pole of the cell. At large angular separations, subpopulations of cells swim away from one source or the other, or along the direction of the geometrical law, with some cells stochastically switching between the three directions. This behavior is shown to arise from a population-level distribution of photoreceptor locations that breaks front-back symmetry of photoreception.