Motility-limited aggregation of mammary epithelial cells into fractal-like clusters

Susan E. Leggett, Zachary J. Neronha, Dhananjay Bhaskar, Jea Yun Sim, Theodora Myrto Perdikari, Ian Y. Wong

Research output: Contribution to journalArticlepeer-review


Migratory cells transition between dispersed individuals and multicellular collectives during development, wound healing, and cancer. These transitions are associated with coordinated behaviors as well as arrested motility at high cell densities, but remain poorly understood at lower cell densities. Here, we show that dispersed mammary epithelial cells organize into arrested, fractal-like clusters at low density in reduced epidermal growth factor (EGF). These clusters exhibit a branched architecture with a fractal dimension of Df = 1.7, reminiscent of diffusion-limited aggregation of nonliving colloidal particles. First, cells display diminished motility in reduced EGF, which permits irreversible adhesion upon cell–cell contact. Subsequently, leader cells emerge that guide collectively migrating strands and connect clusters into space-filling networks. Thus, this living system exhibits gelation-like arrest at low cell densities, analogous to the glass-like arrest of epithelial monolayers at high cell densities. We quantitatively capture these behaviors with a jamming-like phase diagram based on local cell density and EGF. These individual to collective transitions represent an intriguing link between living and nonliving systems, with potential relevance for epithelial morphogenesis into branched architectures.

Original languageEnglish (US)
Pages (from-to)17298-17306
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number35
StatePublished - Aug 27 2019
Externally publishedYes


  • Collective migration
  • Gelation
  • Jamming

ASJC Scopus subject areas

  • General


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