Collective cell movement occurs when two or more cells that retain their cell-cell junctions move together across a two-dimensional (2D) layer of extracellular matrix (ECM) or through a three-dimensional (3D) interstitial tissue scaffold (Friedl and Gilmour, 2009; Friedl et al., 2004; Lecaudey and Gilmour, 2006; Rorth, 2007). Time-lapse and morphological analyses suggest that collective cell movement is relevant for many processes in morphogenesis, tissue repair, and cancer invasion and metastasis (Christiansen and Rajasekaran, 2006; Friedl et al., 1995; Lecaudey and Gilmour, 2006; Vaughan and Trinkaus, 1966; Weijer, 2009). Collective cell dynamics give rise to complex changes in multicellular tissue structures, including epithelial regeneration, the sprouting of vessels and ducts in angiogenesis and branching morphogenesis, and the deregulated invasion of cell masses during cancer progression and consecutive tissue destruction.

Similarly to single-cell migration, collective cell movement results from actomyosin polymerization and contractility coupled to cell polarity; however, there are some key differences. Single-cell migration through interstitial tissue is a cyclical five-step process, comprising cell polarization and protrusion of the leading edge (driven by the actin cytoskeleton), followed by attachment of the leading edge to the substrate, proteolytic degradation of tissue components that physically confine the cell body, actomyosin contraction (leading to tension along the length axis) and, finally, forward sliding of the cell rear (Friedl and Wolf, 2009; Lauffenburger and Horwitz, 1996). Whereas these principles are retained in collective cell movement, the main modification is that the cells remain coupled by cell-cell junctions at the leading edge as well as in lateral regions and inside the moving cell group (Friedl at el., 2004; Lecaudey and Gilmour, 2006; Rorth, 2007). Consequently,