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Emiliano Perez Ipiña
Emiliano Perez Ipiña

How Cellular Footprints Guide Migration

Cells modify their environment as they move
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Cells don’t just move across their environment—they reshape it as they go, leaving footprints that can strongly influence their future motion. A central goal of my research is to understand how these feedbacks between cell motility and the environment generate new migration strategies in both single cells and collectives.

HT-1080 fibrosarcoma epithelial cell moving on the extracellular matrix.
HT-1080 fibrosarcoma epithelial cell moving on the extracellular matrix. Developmental cell, 56(6), 826-841

Cells use their footprints to change their migration strategies
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In my recent research, I explored how cells can change their migration strategies by interacting with molecular footprints they leave behind. My work builds on studies showing that migrating cells leave molecular footprints on the ECM, which can induce oscillatory motion.

We developed a mechanistic framework that couples cell shape, a deposited footprint, and intracellular polarity signaling. In the model, a phase‑field description of the cell is linked to a polarity module in which local contact with the footprint activates Rac1, biasing protrusion toward previously explored regions. This creates a positive feedback loop: the cell moves, deposits more footprint, and becomes more likely to move along that path again.

Cells moving along a linear track exhibit oscillatory behavior due to interactions with their own footprints.

Geometry plays a central role. On 1D micropatterned stripes, our model reproduces oscillations whose amplitude grows as cells repeatedly revisit their own tracks.

Cells moving along a linear track exhibit oscillatory behavior due to interactions with their own footprints. Cells moving along a linear track exhibit oscillatory behavior due to interactions with their own footprints.
Two motility modes. Left: the cell oscillates, turning at the edge of its footprint, with the oscillation amplitude increasing over time. Right: the cell advances persistently in one direction into areas it has not previously visited.

By varying two key factors— such as the rate cells deposit footprint—we find sharp transitions among confined motion, oscillatory back‑and‑forth motion, and persistent exploration. Small parameter changes can therefore produce large behavioral shifts, suggesting that modest biochemical or mechanical regulation may toggle a cell between being trapped and being exploratory.

Gromit frantically lays down train tracks just ahead of a speeding locomotive. From Wallace & Gromit: The Wrong Trousers (1993).
Gromit frantically lays down train tracks just ahead of a speeding locomotive. From Wallace & Gromit: The Wrong Trousers (1993).

In 2D, the same basic mechanism yields two distinct outcomes: circularly confined trajectories that slowly expand, and fully exploratory paths that escape confinement. We revisited experiments on 2D substrates and observed both expanding circular motion and exploratory migration, consistent with the model’s predictions.

Cells moving on a 2D substrate exhibit varying exploratory behaviors depending on how quickly they modify their environment.
Cells on a 2D substrate display different exploratory behaviors depending on how rapidly they modify their environment.

Overall, our results support a simple principle with broad implications: cells can use their own footprints to control their migration strategy.

  • Perez Ipiña, E., d’Alessandro, J., Ladoux, B., Camley, B. A. Deposited footprints let cells switch between confined, oscillatory, and exploratory migration. Proceedings of the National Academy of Sciences 121.22 (2024): e2318248121 link.