TY - JOUR
T1 - Motility-limited aggregation of mammary epithelial cells into fractal-like clusters
AU - Leggett, Susan E.
AU - Neronha, Zachary J.
AU - Bhaskar, Dhananjay
AU - Sim, Jea Yun
AU - Perdikari, Theodora Myrto
AU - Wong, Ian Y.
N1 - Funding Information:
We thank C. Franck, T. M. Powers, and J. X. Tang for careful readings; D. A. Haber for the inducible MCF-10A cell lines; and R. J. Giedt and R. Weissleder for the MDA-MB-231 GFP-H2B cell line. This work was supported by NIH Grants T32ES007272, P30GM110759, and R21CA212932 and by Brown University (DiMase Summer Fellowship, Karen T. Romer Undergraduate Research and Teaching Award, and Start-Up Funds).
Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.
PY - 2019/8/27
Y1 - 2019/8/27
N2 - 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.
AB - 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.
KW - Collective migration
KW - Gelation
KW - Jamming
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U2 - 10.1073/pnas.1905958116
DO - 10.1073/pnas.1905958116
M3 - Article
C2 - 31413194
AN - SCOPUS:85071401785
SN - 0027-8424
VL - 116
SP - 17298
EP - 17306
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 35
ER -