Modeling the dynamics of dendritic actin waves in living cells

Abstract

The actin cytoskeleton in living cells exhibits a high degree of capacity for dynamic self-organization. Recent experiments have observed propagating actin waves in Dictyostelium cells recovering from complete depolymerization of their actin cytoskeleton. The propagation of these waves appear to be dependent on a programmed recruitment of a few proteins that control actin assembly and disassembly. Such waves also arise spontaneously along the plasma membrane of the cell, and it has been suggested that actin waves enable the cell to scan a surface for particles to engulf. Based on known molecular components involved in wave propagation, we present and study a minimal reaction-diffusion model for actin wave production observed in recovering cells.

Fronts and waves of actin polymerization in a bistability-based mechanism of circular dorsal ruffles

“…This provides cells with an inherently robust machinery for efficient macropinocytosis. In contrast, cell-substrate actin waves, such as those in neutrophils20 and Dictyostelium discoideum 23272850, which are involved in cell motility, adhesion and phagocytosis, do not have this requirement3. Consequently, those waves do not close back to points23.…”

“…It is known nevertheless, that CDRs constitute a type of actin wave, that is, a propagating wavefront of actin polymerization at the dorsal cell side 9 16 17 . Actin waves have been observed at the ventral cell side or the cell periphery before 18 19 20 21 22 23 24 and have been studied via reaction–diffusion models in the context of excitable 17 25 26 , wave ustable 27 and bistable 28 29 dynamics, as well as in terms of actin-membrane shape feedback 16 30 31 . However, the phenomenology that incorporates the initial expansion of a circular wavefront from a localized initiation spot, eventual contraction, and ultimate collapse of which the latter process underlies the endocytotic function of CDRs, is unique and currently neither understood nor captured (as a whole) by any existing modelling attempt.…”

Why a Large-Scale Mode Can Be Essential for Understanding Intracellular Actin Waves

“…Yet, in general, RD equations are not subjected to the conservation of mass constraint although often some of the components are conserved, for example, when they represent two different forms of the same protein [ 83 ]. In other cases, the actin is conserved as it is converted from monomeric to filamentous forms and back, see for example [ 58 , 84 ]. In what follows, we address the qualitative role of conservation, which is reflected by the existence of a large scale mode, on the dynamics of IAW, using as much as possible generic principles, i.e., extracting conclusions that are qualitatively independent of the specific molecular details that are included in the model.…”

Collective membrane dynamics emerging from curvature-dependent spatial coupling

“…Many different models have been proposed for waves of actin, most of which are based on reactiondiffusion mechanism [3,4] or its variants with additional factors including cytoplasmic flow [5], myosin-dependent actin transport [6,7] and motor-independent treadmilling [8,9]. Models with actin transport or treadmilling are likely not directly applicable to the actin waves observed in Dictyostelium [10,11] or immune cells [12], where sequential cycles of dendritic actin assembly and disassembly are involved [13]. These actin-centric wave models differ significantly in terms of whether actin provides both positive and negative feedbacks [14], positive feedbacks alone with an unknown diffusing inhibitor [15], or negative feedbacks alone with an upstream activator [4].…”