About the author

Dan Rhoads

Dan is a postdoc working at the University of Cyprus in developmental biology. He has a BSc in molecular biology and a PhD pharmacology and biochemistry.

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Here’s one of my favorite journal articles from the past year – an elegant study by Natalie Andrew and Robert Insall published in Nature Cell Biology: Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions. From the introduction:

We have made detailed, quantitative observations of Dictyostelium cells chemotaxing in shallow gradients, which contradict current models in several ways (see Supplementary Information, Fig. S1): first, new pseudopods are made in spatially restricted sites by splitting of the leading edge; second, the timing and direction of these new pseudopods are random, so they cannot correct the cell’s direction; and third, the survival and retraction of pseudopods are spatially controlled, suggesting an alternative mechanism of chemotaxis.

This model is very similar to the mechanism of growth cone guidance, where random protrusions are constantly exploring the cell’s surroundings, ‘tasting’ for attractant or repellant cues. These cues either stabilize or destabilize one side of the growth cone or pseudopod over the other side, causing the cell to turn one way or another. This isn’t a new concept (having been addressed in neutrophils previously – Arrieumerlou and Meyer, 2005), but Andrew and Insall formalize the case for biased choices in chemotaxis in Dictyostelium very nicely (Figure 1, below).

The neat visual here is that the Dictyostelium cell does indeed continually split its dominant pseudopod in half every so often, as it seeks for and exploits whatever signals are offered to it. It is a nice example of the combination of exploratory and exploitative behaviors (or stochastic and deterministic behaviors) that I’m so fond of describing. Rather like everything in this world we live in, even the question of finding one’s destiny in human affairs, there is a tremendous amount of chance in what cues any given cell is introduced to, but there appear to be very defined ways of establishing bias between one direction and another.

Interestingly, Andrew and Insall also examined the role of PI-3 Kinase in the dynamics of pseudopod generation (Figure 5, below)

By comparing cells treated and untreated with the PI-3 Kinase inhibitor LY294002, Andrew and Insall found that the cells were just as motile, but formed new pseudopods much more slowly. Presumably, this effect would reduce the cell’s ability to quickly respond to fluctuating gradients. And as the authors suggest, mechanisms that modulate existing turning behavior, rather than mechanisms that directly specify new directions, are more appropriate for small, noisy, or fluctuating signals. Furthermore, restricting new pseudopods to the immediate vicinity of existing ones could alone be sufficient to cause directional persistence and could be involved in cell polarization.

Commentary:

What’s interesting about this study is the obvious pattern involved. It’s not completely deterministic, nor is it completely random. It’s biased, and limited by the explainable molecular interactions within specific subcellular domains. From this standpoint, the biased choices of motile cells bears striking resemblance to patterns that are pervasive throughout all of biology, and even human affairs. It is random and chaotic at first glance, but somewhat ordered upon further inspection, and ultimately at the mercy of extrinsic cues.

References:

• Andrew N, Insall RH. Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions. Nat Cell Biol. 9(2):193-200 (2007). doi:10.1038/ncb1536
• Arrieumerlou C, Meyer T. A local coupling model and compass parameter for eukaryotic chemotaxis. Dev. Cell 8:215–227 (2005). doi:10.1016/j.devcel.2004.12.007