Active gel theory for cell migration with two myosin isoforms

Abstract

Myosin II molecular motors slide actin filaments relatively to each other and are essential for force generation, motility and mechanosensing in animal cells. For non-muscle cells, evolution has resulted in three different isoforms, which have different properties concerning the motor cycle and also occur in different abundances in the cells, but their respective biological and physical roles are not fully understood. Here we use active gel theory to demonstrate the complementary roles of isoforms A and B for cell migration. We first show that our model can be derived both from coarse-graining kinetic equations and from nonequilibrium thermodynamics as the macroscopic limit of a two-component Tonks gas. We then parametrize the model and show that motile solutions exist, in which the more abundant and more dynamic isoform A is localized to the front and the stronger isoform B to the rear, in agreement with experiments. Exploring parameter space beyond the isoform parameters typical for animal cells, we also find cell oscillations in length and velocity, which might be realized for genetically engineered systems. We also describe an analytical solution for the stiff limit, which then is used to calculate a state diagram, and the effect of actin polymerization at the boundaries, that leads to an imperfect pitchfork bifurcation. Our findings highlight the importance of including isoform-specific molecular details to describe whole cell behavior.

Revtex, 14 pages, 9 figures, 63 references

References in corpus (13)

• Generic theory of active polar gels: a paradigm for cytoskeletal dynamics
• One dimensional cell motility patterns
• Instabilities in the transient response of muscle
• Stochastic dynamics of small ensembles of non-processive molecular motors: the parallel cluster model
• Morphological Instability and Dynamics of Fronts in Bacterial Growth Models with Nonlinear Diffusion
• Mechanics of motility initiation and motility arrest in crawling cells
• A density functional theory for general hard-core lattice gases
• Nonideal Reaction-Diffusion Systems: Multiple Routes to Instability
• Sensitivity of small myosin II ensembles from different isoforms to mechanical load and ATP concentration
• Optogenetic switching of migration of contractile cells
• Active gel model for one-dimensional cell migration coupling actin flow and adhesion dynamics
• Optogenetic control of intracellular flows and cell migration: a comprehensive mathematical analysis with a minimal active gel model
• Cell motility as an energy minimization process