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Collective Cell Migration in Microstructured Environments

Collective cell migration is a key element in morphogenesis, cancer formation and wound healing. The multicellular dynamics of epithelial cell layers were studied in experiment and theory over the last years. Yet little is known about cell patches of finite size that should lead over from single cell behavior to collective motion. Here we study the migration and proliferation of small assemblies of epithelial cells (5-23 cells initially). Cells are released at defined time using removable poly(ethylene glycol)-dimethlacrylate (PEG- DMA) stencils with circular apertures, wherein cells were seeded. Using time-lapse microscopy we determine cell number, cell patch area and shape of multiple patches in parallel. We confirm exponential growth in cell number but find the area of the patches expanding faster than exponential in the early phase. The area is, however, well-described if cell proliferation is superimposed by elastic area dilation assuming that the cell groups were initially compressed. The elastic relaxation time is of the same order as the measured doubling time. Furthermore, analysis of the center-of-mass movement of the patches reveals bursts of directed motion, which coincide with asymmetric cell growth. In these cases the contours of the patches seem to result from a tug-of-war like scenario of opposing leader cells.

A.-K. Marel, A. Piera Alberola, J. O. Rädler
Proliferation and collective migration of small cell groups released from circular patches
Biophysical Reviews and Letters Vol. 7, Nos. 1 & 2 (2012) 15–28.