Collective cell migration has distinct directionality and speed dynamics |
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| Authors: | Yan Zhang Guoqing Xu Rachel M Lee Zijie Zhu Jiandong Wu Simon Liao Gong Zhang Yaohui Sun Alex Mogilner Wolfgang Losert Tingrui Pan Francis Lin Zhengping Xu Min Zhao |
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| Institution: | 1.Department of Dermatology,University of California,Davis,USA;2.Institute of Environmental Medicine,Zhejiang University School of Medicine,Hangzhou,China;3.Micro-Nano Innovations (MiNI) Laboratory, Department of Biomedical Engineering,University of California,Davis,USA;4.Department of Physics and Astronomy,University of Manitoba,Winnipeg,Canada;5.Department of Applied Computer Science,University of Winnipeg,Winnipeg,Canada;6.Department of Physics,University of Maryland,College Park,USA;7.Seven Oaks Hospital Wellness Institute,Winnipeg,Canada;8.The First Affiliated Hospital of Henan University of Science and Technology,Luoyang,China;9.Courant Institute and Department of Biology,New York University,New York,USA;10.Department of Ophthalmology and Vision Science,University of California,Davis,USA |
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| Abstract: | When a constraint is removed, confluent cells migrate directionally into the available space. How the migration directionality and speed increase are initiated at the leading edge and propagate into neighboring cells are not well understood. Using a quantitative visualization technique—Particle Image Velocimetry (PIV)—we revealed that migration directionality and speed had strikingly different dynamics. Migration directionality increases as a wave propagating from the leading edge into the cell sheet, while the increase in cell migration speed is maintained only at the leading edge. The overall directionality steadily increases with time as cells migrate into the cell-free space, but migration speed remains largely the same. A particle-based compass (PBC) model suggests cellular interplay (which depends on cell–cell distance) and migration speed are sufficient to capture the dynamics of migration directionality revealed experimentally. Extracellular Ca2+ regulated both migration speed and directionality, but in a significantly different way, suggested by the correlation between directionality and speed only in some dynamic ranges. Our experimental and modeling results reveal distinct directionality and speed dynamics in collective migration, and these factors can be regulated by extracellular Ca2+ through cellular interplay. Quantitative visualization using PIV and our PBC model thus provide a powerful approach to dissect the mechanisms of collective cell migration. |
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