# Trade-off between branching and polarity controls decision-making during cell migration

## TL;DR

This paper explores how cells balance branching and directional movement when navigating complex environments.

## Contribution

The study introduces a theoretical model showing how protrusions compete to guide cell movement in complex geometries.

## Key findings

- Macrophages and endothelial cells show different migratory regimes on hexagonal networks.
- A trade-off exists between branching and migration speed in cell movement.
- Multiple protrusions aid in environmental exploration but reduce long-range migration efficiency.

## Abstract

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.

Highly branched cells require fine-tuning of polarity and shape dynamics to ensure balance between exploration and migration.