Search

Background: Organisms, at scales ranging from unicellular to mammals, have been known to exhibit foraging behavior described by random walks whose segments confirm to Lévy or exponential distributions. For the first time, we present evidence that single cells (mammary epithelial cells) that exist in multi-cellular organisms (humans) follow a bimodal correlated random walk (BCRW). Methodology/Principal Findings: Cellular tracks of MCF-10A pBabe, neuN and neuT random migration on 2-D plastic substrates, analyzed using bimodal analysis, were found to reveal the BCRW pattern. We find two types of exponentially distributed correlated flights (corresponding to what we refer to as the directional and re-orientation phases) each having its own correlation between move step-lengths within flights. The exponential distribution of flight lengths was confirmed using different analysis methods (logarithmic binning with normalization, survival frequency plots and maximum likelihood estimation). Conclusions/Significance: Because of the presence of non-uniform turn angle distribution of move step-lengths within a flight and two different types of flights, we propose that the epithelial random walk is a BCRW comprising of two alternating modes with varying degree of correlations, rather than a simple persistent random walk. A BCRW model rather than a simple persistent random walk correctly matches the super-diffusivity in the cell migration paths as indicated by simulations based on the BCRW model. [ABSTRACT FROM AUTHOR]

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 pseudo-thermal 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. [ABSTRACT FROM AUTHOR]