Protrusion of a Virtual Model Lamellipodium by Actin Polymerization: A Coarse-Grained Langevin Dynamics Model

Abstract

We report the development of a coarse-grained Langevin dynamics model of a lamellipodium featuring growing F-actin filaments in order to study the effect of stiffness of the F-actin filament, the G-actin monomer concentration, and the number of polymerization sites on lamellipodium protrusion. The virtual lamellipodium is modeled as a low-aspect-ratio doubly capped cylinder formed by triangulated particles on its surface. It is assumed that F-actin filaments are firmly attached to a lamellipodium surface where polymerization sites are located, and actin polymerization takes place by connecting a G-actin particle to a polymerization site and to the first particle of a growing F-actin filament. It is found that there is an optimal number of polymerization sites for rapid lamellipodium protrusion. The maximum speed of lamellipodium protrusion is related to competition between the number of polymerization sites and the number of available G-actin particles, and the degree of pulling and holding of the lamellipodium surface by non-polymerizing actin filaments. The lamellipodium protrusion by actin polymerization displays saltatory motion exhibiting pseudothermal equilibrium: the lamellipodium speed distribution is Maxwellian in two dimensions but the lamellipodium motion is biased so that the lamellipodium speed in the direction of the lamellipodium motion is much larger than that normal to the lamellipodium motion.

Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries

“…It is believed to be the motor which push the cortical cytoskeleton forward during the process of cell migration. Normally, cells experience a small protrusive pressure that results from osmotic pressure or actin branches stimulated by activated arp2/3 [70]. Recently, time-averaged high protrusive force measured per pillar was 800 pN for NIH 3T3 fibroblasts and diseased cells [71].…”

Biomechanics of actin filaments: A computational multi-level study

“…1a) that rearrange upon polymerization into F-actin. F-actin is the functional form of the protein (Pollard et al, 2000) and it is involved in many cellular processes, as muscle contraction, cell motility, cell division, vesicle and organelle movement, cell signaling, maintenance of cell junctions and cell shape (Gittes et al, 1993;Gov et al, 2006;Howard, 2001;Isambert et al, 1995;Jeon et al, 2008;Kojima et al, 1994;McCullough et al, 2008;Otterbein et al, 2001;Stricker et al, 2010;Tsuda et al, 1996;Yang et al, 2008).…”

Connecting actin polymer dynamics across multiple scales

“…In these simulations, agents behave autonomously and through simple rules prescribed at each time step. The technique is stochastic and can be interpreted as a coarsening of Brownian and Langevin dynamical models [34]. However, agent-based approaches are computationally expensive: at every time step, they specifically account for the movement and interaction of individual molecules, while also assessing the effects of spatial and environmental properties that ultimately result in the emergence of certain large-scale phenomena, such as crowding.…”