Cell density and actomyosin contractility control the organization of migrating collectives within an epithelium.
The mechanisms underlying collective migration are important for understanding development, wound healing, and tumor invasion. Here we focus on cell density to determine its role in collective migration. Our findings show that increasing cell density, as might be seen in cancer, transforms groups from broad collectives to small, narrow streams. Conversely, diminishing cell density, as might occur at a wound front, leads to large, broad collectives with a distinct leader-follower structure. Simulations identify force-sensitive contractility as a mediator of how density affects collectives, and guided by this prediction, we find that the baseline state of contractility can enhance or reduce organization. Finally, we test predictions from these data in an in vivo epithelium by using genetic manipulations to drive collective motion between predicted migratory phases. This work demonstrates how commonly altered cellular properties can prime groups of cells to adopt migration patterns that may be harnessed in health or exploited in disease.
ICCE Institute, Washington University in St. Louis School of Medicine, St. Louis, MO 63110.|Department of Biochemistry and Biophysics, Washington University in St. Louis School of Medicine, St. Louis, MO 63110.|Department of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110.
Andrew J
AJ
Loza
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218.
Sarita
S
Koride
ICCE Institute, Washington University in St. Louis School of Medicine, St. Louis, MO 63110.|Department of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110.
Gregory V
GV
Schimizzi
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218.
Bo
B
Li
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218.
Sean X
SX
Sun
ICCE Institute, Washington University in St. Louis School of Medicine, St. Louis, MO 63110 glongmor@dom.wustl.edu.|Department of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110.|Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218.|Division of Oncology, Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO 63110.
Gregory D
GD
Longmore
D008841:Actin Cytoskeleton / Q000502:physiology; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity; D003198:Computer Simulation; D004330:Drosophila / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
D000205:Actomyosin