Actin polymerization and subcellular mechanics drive nonlocal excitable waves in living cells

Start: 02/02/2015 - 12:00pm
End  : 02/02/2015 - 1:00pm

Applied Math Seminar

Jun Allard (University of California, Irvine)


Traveling waves of the actin have recently been reported in many cell types. Actin is a protein that forms polymers that power cell crawling in immune cells during immune surveillance, skin cells during wound healing, and cancer cells during invasion. Fish keratocyte cells, which usually exhibit rapid and steady crawling, exhibit traveling waves of protrusion when plated on highly adhesive surfaces. We hypothesize that waving arises from a competition between actin polymerization and mature adhesions for VASP, a protein that associates with growing actin barbed ends. We developed a mathematical model of actin protrusion coupled with membrane tension, adhesions and VASP. The model is formulated as a system of partial differential equations with a nonlocal integral term and noise. These equations reveal a mathematical structure in which the system dynamically undergoes a bifurcation between oscillatory and excitable states. Simulations of this model lead to a number of predictions, for example, that overexpression of VASP prevents waving, but depletion of VASP does not increase the fraction of cells that wave. Further experiments confirmed these predictions and provided quantitative data to estimate the model parameters. We thus conclude that the waves are the result of competition between actin and adhesions for VASP, rather than a regulatory biochemical oscillator or mechanical tag-of-war. We hypothesize that this waving behavior contributes to adaptation of cell motility mechanisms in perturbed environments. This is work in collaboration with Erin Barnhart, Julie Theriot, and Alex Mogilner.

Kravis Center 100

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