Pattern formation along signaling gradients driven by active droplet behavior of cell swarms

TY - JOUR

T1 - Pattern formation along signaling gradients driven by active droplet behavior of cell swarms

AU - Ford, Hugh Z

AU - Celora, Giulia L

AU - Westbrook, Elizabeth R

AU - Dalwadi, Mohit P

AU - Walker, Benjamin J

AU - Baumann, Hella

AU - Weijer, Kees

AU - Pearce, Philip

AU - Chubb, Jonathan R.

N1 - © 2025 the Author(s)

PY - 2025/5/27

Y1 - 2025/5/27

N2 - Gradients of extracellular signals organize cells in tissues. Although there are several models for how gradients can pattern cell behavior, it is not clear how cells react to gradients when the population is undergoing 3D morphogenesis, in which cell–cell and cell–signal interactions are continually changing. Dictyostelium cells follow gradients of their nutritional source to feed and maintain their undifferentiated state. Using lightsheet imaging to simultaneously monitor signaling, single-cell, and population dynamics, we show that the cells migrate toward nutritional gradients in swarms. As swarms advance, they deposit clumps of cells at the rear, triggering differentiation. Clump deposition is explained by a physical model in which cell swarms behave as active droplets: cells proliferate within the swarm, with clump shedding occurring at a critical population size, at which cells at the rear no longer perceive the gradient and are not retained by the emergent surface tension of the swarm. The model predicts vortex motion of the cells within the swarm emerging from the local transfer of propulsion forces, a prediction validated by 3D tracking of single cells. This active fluid behavior reveals a developmental mechanism we term “musical chairs” decision-making, in which the decision to proliferate or differentiate is determined by the position of a cell within the group as it bifurcates.

AB - Gradients of extracellular signals organize cells in tissues. Although there are several models for how gradients can pattern cell behavior, it is not clear how cells react to gradients when the population is undergoing 3D morphogenesis, in which cell–cell and cell–signal interactions are continually changing. Dictyostelium cells follow gradients of their nutritional source to feed and maintain their undifferentiated state. Using lightsheet imaging to simultaneously monitor signaling, single-cell, and population dynamics, we show that the cells migrate toward nutritional gradients in swarms. As swarms advance, they deposit clumps of cells at the rear, triggering differentiation. Clump deposition is explained by a physical model in which cell swarms behave as active droplets: cells proliferate within the swarm, with clump shedding occurring at a critical population size, at which cells at the rear no longer perceive the gradient and are not retained by the emergent surface tension of the swarm. The model predicts vortex motion of the cells within the swarm emerging from the local transfer of propulsion forces, a prediction validated by 3D tracking of single cells. This active fluid behavior reveals a developmental mechanism we term “musical chairs” decision-making, in which the decision to proliferate or differentiate is determined by the position of a cell within the group as it bifurcates.

KW - signaling gradients

KW - active droplet

KW - chemotaxis

KW - tissue fluidity

KW - pattern formation

U2 - 10.1073/pnas.2419152122

DO - 10.1073/pnas.2419152122

M3 - Article

C2 - 40392846

SN - 0027-8424

VL - 122

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

IS - 21

M1 - e2419152122

ER -