Doyle et al. report that the movement of cells in a straight line is very similar to that in three dimensions (3D), whereas both differ markedly from 2D movement. Analyses in 1D might therefore provide useful information about cell movement in vivo.
The team made this discovery when they were investigating a new way to apply micropatterns of proteins onto coverslips (for analysis of cell attachment). Previous micropatterning techniques involved the printing of proteins onto gold-plated coverslips. However, while gold is great for protein binding, it's not so great for fluorescent microscopy—it readily absorbs fluorescent emissions. Doyle et al.'s new fluorescence-friendly approach was to coat coverslips with polyvinyl alcohol (PVA), which resists protein and cell binding, and then remove regions of the PVA by laser ablation. Proteins added to the coverslip will then stick to the ablated patterns only.
Among the micropatterns that the team drew were simple straight lines. When extracellular matrix proteins, and then cells, were added to such coverslips the cells started to migrate along the matrix-containing lines. Importantly, the cells' movement looked just like that on 3D fibrillar matrices.
Cells migrating in 2D have a spreading, multi-axial morphology, but on the 1D lines, as in 3D matrices, the cells were uniaxial. Their migration was also more rapid, even at high ligand densities (on 2D surfaces high ligand density slows cells, as they have trouble detaching).
The faster speed is probably explained by the fact that less of the cell is in contact with the surface, so more of its machinery is available to drive the cell forward. Indeed this would explain why Doyle et al. found that movement in 1D and 3D was dependent on myosin II contractility. Cells on 2D surfaces, on the other hand, use most of their myosin to make surface contacts, so actually speed up if contractility is lost.
So is there a future in 2D analyses? Doyle diplomatically suggests that researchers “have to take a closer look at whether or not what's happening in the dish is really what's happening in vivo.” RW
