Stochastic model of receptor-mediated cytomechanics and dynamic morphology of leukocytes

Abstract

The proposed mathematical model investigates the simplified cytomechanics of cell shape change driven by stochastic stimulation from chemosensory receptors. The cytomechanical component of our model describes the dynamical distribution of F-actin and associated forces in an idealized cortical actin network around the cell periphery. The chemosensory component describes the distribution of chemotactic receptors in the cell membrane surrounding the cortex, where bound receptors give rise to an intracellular signal which modulates some property of the cortical network. As in our earlier models, an account is made for (1) the reactive, contractive properties of cortical actin, but here also for a stress induced by curvature of the cortex-membrane complex which carries an effective surface tension, and (2) statistical fluctuations in receptor binding, but generalized here to include statistical fluctuations in the spatial distribution of receptors, entirely determined by the additional prescription of membrane diffusion coefficients along with total receptor number, receptor binding rate constants and the local concentration field of chemotactic factor. We simplify the analysis by restricting the model to a prototype in which viscous stresses in the cortical network are negligible and the radial extension of the cell cortex is a prescribed function of the cortical actin concentration. We assume in particular that the assembly rate of cortical actin depends on the local density of bound receptors. These assumptions lead to a 4th-order parabolic differential equation on the unit circle coupled to a system of stochastic differential equations. We characterize via bifurcation analysis, stochastic simulations, and analytical correlation functions the spatial-temporal pattern of cell morphology under the influence of fluctuations in the bound receptor distribution for the case of a uniform concentration field of chemotactic factor. In addition to addressing the biological significance of our model, we remark on its relevance to the generic problem of the influence of correlated stochastic perturbations on spatial patterns in morphogenetic media.