title: New wrinkling substrate assay reveals traction force fields of leader and follower cells undergoing collective migration.
abstract: Physical forces play crucial roles in coordinating collective migration of epithelial cells, but details of such force-related phenomena remain unclear partly due to the lack of robust methodologies to probe the underlying force fields. Here we develop a method for fabricating silicone substrates that detect cellular traction forces with a high sensitivity. Specifically, a silicone elastomer is exposed to oxygen plasma under heating. Removal of the heat shrinks the substrate so as to reduce its critical buckling strain in a spatially uniform manner. Thus, even small cellular traction forces can be visualized as micro-wrinkles that are reversibly emerged on the substrate in a direction orthogonal to the applied forces. Using this technique, we show that so-called leader cells in MDCK-II cell clusters exert significant magnitudes of traction forces distinct from those of follower cells. We reveal that the direction of traction forces is highly correlated with the long axis of the local, individual cells within clusters. These results suggest that the force fields in collective migration of MDCK-II cells are predominantly determined locally at individual cell scale rather than globally at the whole cell cluster scale.
authors.affiliation: Department of Nanopharmaceutical Sciences, Nagoya Institute of Technology, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: Department of Nanopharmaceutical Sciences, Nagoya Institute of Technology, Japan; Division of Bioengineering, Osaka University, Japan.
authors.forename: Tsubasa S
authors.initials: TS
authors.lastname: Matsui
authors.affiliation: Department of Nanopharmaceutical Sciences, Nagoya Institute of Technology, Japan; Division of Bioengineering, Osaka University, Japan. Electronic address: deguchi@me.es.osaka-u.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Deguchi
mesh_terms: D000818:Animals; D017209:Apoptosis; D001672:Biocompatible Materials / Q000737:chemistry; D002448:Cell Adhesion; D002465:Cell Movement; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology*; D061985:Madin Darby Canine Kidney Cells; D012825:Silicon / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D012825:Silicon
keywords: Collective cell migration; Epithelial cells; MDCK-II cells; Traction force microscopy; Wrinkling substrate assay