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      An efficient, nonlinear stability analysis for detecting pattern formation in reaction diffusion systems

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          Abstract

          Reaction diffusion systems are often used to study pattern formation in biological systems. However, most methods for understanding their behavior are challenging and can rarely be applied to complex systems common in biological applications. I present a relatively simple and efficient, non-linear stability technique that greatly aids such analysis when rates of diffusion are substantially different. This technique reduces a system of reaction diffusion equations to a system of ordinary differential equations tracking the evolution of a large amplitude, spatially localized perturbation of a homogeneous steady state. Stability properties of this system, determined using standard bifurcation techniques and software, describe both linear and non-linear patterning regimes of the reaction diffusion system. I describe the class of systems this method can be applied to and demonstrate its application. Analysis of Schnakenberg and substrate inhibition models is performed to demonstrate the methods capabilities in simplified settings and show that even these simple models have non-linear patterning regimes not previously detected. Analysis of a protein regulatory network related to chemotaxis shows its application in a more complex setting where other non-linear methods become intractable. Predictions of this method are verified against results of numerical simulation, linear stability, and full PDE bifurcation analyses.

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          A theory of biological pattern formation

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              Wave-pinning and cell polarity from a bistable reaction-diffusion system.

              Motile eukaryotic cells polarize in response to external signals. Numerous mechanisms have been suggested to account for this symmetry breaking and for the ensuing robust polarization. Implicated in this process are various proteins that are recruited to the plasma membrane and segregate at an emergent front or back of the polarizing cell. Among these are PI3K, PTEN, and members of the Rho family GTPases such as Cdc42, Rac, and Rho. Many such proteins, including the Rho GTPases, cycle between active membrane-bound forms and inactive cytosolic forms. In previous work, we have shown that this property, together with appropriate crosstalk, endows a biochemical circuit (Cdc42, Rac, and Rho) with the property of inherent polarizability. Here we show that this property is present in an even simpler system comprised of a single active/inactive protein pair with positive feedback to its own activation. The simplicity of this minimal system also allows us to explain the mechanism using insights from mathematical analysis. The basic idea resides in a well-known property of reaction-diffusion systems with bistable kinetics, namely, propagation of fronts. However, it crucially depends on exchange between active and inactive forms of the chemicals with unequal rates of diffusion, and overall conservation to pin the waves into a stable polar distribution. We refer to these dynamics as wave-pinning and we show that this phenomenon is distinct from Turing-instability-generated pattern formation that occurs in reaction-diffusion systems that appear to be very similar. We explain the mathematical basis of the phenomenon, relate it to spatial segregation of Rho GTPases, and show how it can account for spatial amplification and maintenance of polarity, as well as sensitivity to new stimuli typical in polarization of eukaryotic cells.
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                Author and article information

                Journal
                2012-06-09
                2013-05-22
                Article
                1206.1985
                0ee53e62-9908-4564-bf8e-1ec51880a08d

                http://arxiv.org/licenses/nonexclusive-distrib/1.0/

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                Custom metadata
                35K57, 92C15, 92C42
                math.AP nlin.PS

                Analysis,Nonlinear & Complex systems
                Analysis, Nonlinear & Complex systems

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