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Collective Movement of Epithelial Cells on a Collagen Gel Substrate

Hisashi Haga ^*, Chikako Irahara ^*, Ryo Kobayashi , Toshiyuki Nakagaki  and Kazushige Kawabata ^*

^* Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan; Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526, Japan; and Division of Innovative Research, Creative Research Initiative "Sosei", Hokkaido University, Sapporo 001-0021, Japan

Correspondence: Address reprint requests to Hisashi Haga, PhD, Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan. Tel.: 81-11-706-4909; Fax: 81-11-706-4992; E-mail: haga{at}sci.hokudai.ac.jp.

Collective cell movement acts as an efficient strategy in many physiological events, including wound healing, embryonic development, and morphogenesis. We found that epithelial cells (Madin-Darby canine kidney cell) migrated collectively along one direction on a collagen gel substrate. Time-lapse images of Madin-Darby canine kidney cells cultured on type-I collagen gels and glass substrates were captured by phase contrast microscopy equipped with an incubation system. On the gel substrate, the directions of cell movement gradually converged on one direction as the number of cells increased, whereas the cells moved randomly on the glass substrate. We also observed "leader" cells, which extended large lamellae and were accompanied by many "follower" cells, migrating in the direction of oriented collagen fibers. The mean-squared displacement of each cell movement and the spatial correlation function calculated from the spatial distribution of cell velocity were obtained as functions of observation time. In the case of the gel substrate, the spatial correlation length increased gradually, representing the collectiveness of multicellular movement.