Physics versus Signaling

This is a very simple paper that attempts to answer a simple question – does physics play any role in regulating cell siganling. As cell biologists we generally like to think of signaling cascades as regulating cellular processes. We consider that an extracellular ligand binds a receptor triggering a cascade that results in some cellular behavior. The Odde lab however takes a different approach and proposes that physics, specifically cell size and shape play an important role in regulating cell signaling. Using mathematical models they show that if two signals are spatially segregated, there will be a sharp drop off in activity. In the theoretical portion of the paper they use the example of a protein that is phosphorylated by a membrane bound kinase and dephosphorylated by a cytosolic phosphatase under a variety of situations (a migrating cell is depicted to the left). While it seems obvious that if you bring the membrane close together you will increase the local kinase concentration/activity and decrease the local phosphatase concentration/activity, I don’t remember it being said before. Finally they use their model to recapitulate Cdc42 activity as was experimentally shown by Nalbant et al. (right), but unfortunately this is the only experimental evidence they site.

This is certainly an interesting take on signaling however, it raises a chicken or the egg type of question. Do we know as a matter of fact that Cdc42 does not contribute to cell “flattening” where it is active? Similarly they use a migrating cell in their models as an example of a situation where one would have spatially segregated signaling but as far as I can tell it is difficult to ascertain whether cellular physics lead to signaling or if signaling precedes the physics.


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