Mechano-chemical feedbacks govern stochastic dynamics of actin networks in eukaryotic cells

6 June 2012
Garegin Papoian

Actin polymerization in vivo is regulated spatially and temporally by a web of signalling proteins. We developed detailed physico-chemical, stochastic models of lamellipodia and filopodia, which are projected by eukaryotic cells during cell migration, and contain dynamically remodelling actin meshes and bundles. In a recent work we studied how molecular motors regulate growth dynamics of elongated organelles of living cells. We determined spatial distributions of motors in such organelles, corresponding to a basic scenario when motors only walk along the substrate, bind, unbind, and diffuse. We developed a mean field model, which quantitatively reproduces elaborate stochastic simulation results as well as provides a physical interpretation of experimentally observed distributions of Myosin IIIa in stereocilia and filopodia. The mean field model showed that the jamming of the walking motors is conspicuous, and therefore damps the active motor flux. However, when the motor distributions are coupled to the delivery of actin monomers towards the tip, even the concentration bump of G-actin that they create before they jam is enough to speed up the diffusion to allow for severalfold longer filopodia. We found that the concentration profile of G-actin along the filopodium is rather non-trivial, containing a narrow minimum near the base followed by a broad maximum. For efficient enough actin transport, this non-monotonous shape is expected to occur under a broad set of conditions. We also find that the stationary motor distribution is universal for the given set of model parameters regardless of the organelle length, which follows from the form of the kinetic equations and the boundary conditions.

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