Sota Tate1, Matome Imai1, Natsuki Matsushita2, Emi K Nishimura3, Shigeki Higashiyama4, Daisuke Nanba5. 1. Department of Biochemistry and Molecular Genetics, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan. 2. Translational Research Center, Ehime University Hospital, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan. 3. Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. 4. Department of Biochemistry and Molecular Genetics, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan; Division of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan. 5. Department of Biochemistry and Molecular Genetics, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan; Division of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan; Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: nanbscm@tmd.ac.jp.
Abstract
BACKGROUND: Collective motion of keratinocytes is involved in morphogenesis, homeostasis, and wound healing of the epidermis. Yet how the collective motion of keratinocytes emerges from the behavior of individual cells is still largely unknown. OBJECTIVE: The aim of this study was to find the cellular behavior that links single and collective motion of keratinocytes. METHODS: We investigated the behavior of two-cell colonies of HaCaT keratinocytes by a combination of time-lapse imaging and image processing. RESULTS: The two-cell colonies of HaCaT cells were formed as a contacted pair of keratinocyte clones. Image analysis and cell culture experiments revealed that the rotational speed of two-cell colonies was positively associated with their proliferative capacity. α6 integrin was required for the rotational motion of two-cell keratinocyte colonies. We also confirmed that two-cell colonies of keratinocytes predominantly exhibited the rotational, but not translational, motion, two modes of motion in a contact pair of rotating objects. CONCLUSION: The rotational motion is the primary motion of two-cell keratinocyte colonies and its speed is positively associated with their proliferative capacity. This study suggests that the assembly of rotating keratinocytes generates the collective motion of proliferative keratinocytes during morphogenesis and wound healing of the epidermis.
BACKGROUND: Collective motion of keratinocytes is involved in morphogenesis, homeostasis, and wound healing of the epidermis. Yet how the collective motion of keratinocytes emerges from the behavior of individual cells is still largely unknown. OBJECTIVE: The aim of this study was to find the cellular behavior that links single and collective motion of keratinocytes. METHODS: We investigated the behavior of two-cell colonies of HaCaT keratinocytes by a combination of time-lapse imaging and image processing. RESULTS: The two-cell colonies of HaCaT cells were formed as a contacted pair of keratinocyte clones. Image analysis and cell culture experiments revealed that the rotational speed of two-cell colonies was positively associated with their proliferative capacity. α6 integrin was required for the rotational motion of two-cell keratinocyte colonies. We also confirmed that two-cell colonies of keratinocytes predominantly exhibited the rotational, but not translational, motion, two modes of motion in a contact pair of rotating objects. CONCLUSION: The rotational motion is the primary motion of two-cell keratinocyte colonies and its speed is positively associated with their proliferative capacity. This study suggests that the assembly of rotating keratinocytes generates the collective motion of proliferative keratinocytes during morphogenesis and wound healing of the epidermis.