Slime mold: it's repulsive and slimy, isn't actually a fungus and can't possibly be of any use. And yet, slime molds are serving as excellent model systems for one of the most ubiquitous and important cellular phenomena, cell migration. Cell migration is critical for wound healing, embryonic development and the immune response, among other processes – and while the molecular mechanisms driving cell migration have been extensively studied, the physical mechanics of cell migration remain largely a mystery. So, how could slime molds help us to understand cell migration? For one, slime molds are very good at moving around. A plasmodial slime mold, like the yellow Physarum, is a single huge multinucleate cell that rhythmically shuttles its cytoplasm through its own tubular network. Smaller slime mold amoebae also exhibit periodic movement of their cytoplasm, which coincides with a tremendous increase in cell migration speed. Given the motility of slime mold amoeba and slime mold's large cell sizes, they make an excellent system for studying the mechanics of cell migration.
Owen Lewis of the University of Utah, USA, and colleagues at the University of California in San Diego and Davis took advantage of the benefits of working with slime mold to examine how cytoplasmic flow, cytoskeletal contraction and substrate adhesion contribute to cell locomotion. The researchers took a two-pronged approach to their study, coupling measurements of cytoplasmic flow, traction and substrate displacement taken from real slime mold amoeboid cells with a computational approach where they incorporated those data into a model of a slime mold cell that included additional parameters for flow, cytoskeletal contraction, and adhesion.
The slime mold's movement was characterized by a traveling wave of cytoplasmic flow and a traveling wave of contraction. These waves had equal periods, but a phase lag of about one-third of a cycle. This produces a cycle of traveling contracting and expanding regions, moving from anterior to posterior. Earlier studies had suggested that this pattern of flow alone could produce forward movement – but Lewis and colleagues’ data showed that the observed flow patterns in the slime mold cells would actually tend to produce backward movement without other influences.
With this apparent paradox in hand, the researchers used their computational model to see whether one of the other parameters they modeled was critical for forward motion. When they varied the adhesion parameters, they found that not only is hydrodynamic flow essential for locomotion but also the transmission of the flow stress to the substrate via adhesion was necessary. The phase of adhesive forces relative to flow stress was key – flow and adhesion must be strictly coordinated if the cell is to move anywhere quickly.
Lewis and colleagues were also able to test several other hypotheses about amoeba motility by using their integrated experimental dataset and computational model. They showed not only that slime mold movement is a precisely coordinated dance of cellular flow and adhesion but also – and perhaps more importantly – the utility of using this slimy system for understanding cell migration.