Computer Simulations of Mechano-Chemical Networks Choreographing Actin Dynamics in Cell Motility - Computational Modeling of Biological Systems - page 247

persistent and fast motion [ 65 , 77 , 83 , 84 ]. Moreover, despite the complexity of actin-
based motility, it has been found that simplified models with reconstituted in vitro
system consisting of only the most essential elements can offer great insight on the
physics behind actin-based motility [ 81 , 85 ]. Thus, it should be feasible to construct
physically based simple computational models with a relatively small number of
components to study actin-based motility. Taking into account these considerations,
a recent 3D model of the growth dynamics of lamellipodia-like mesh network was
developed to investigate how capping and anti-capping proteins regulate growth
dynamics of such branched filamentous networks [ 35 , 80 ](seeFig. 3 for a schematic
illustration of the model). It was observed in the stochastic simulations that with
introducing capping proteins and anti-capping proteins, the density of membrane
leading edge filaments changes correspondingly, which in turn leads to the change
of the number of G-actin monomers available for polymerization and the load on
polymerizing filaments. Thus, the density of leading edge filaments is a simple
but critical quantity controlling protrusion dynamics, since it governs both the
pool of G-actin monomers available for polymerization and the instantaneous
load polymerizing filaments experience. By observing how the density of filament
changes with the varying concentration of regulatory proteins, one can gain valuable
insight on how the regulatory proteins such as capping and anti-capping proteins
control the actin dynamics in lamellipodial-like branched network.
Lamellipodial protrusion dynamics is controlled by complex mechano-chemical
feedbacks. The interplay between molecular processes such as the diffusion and
reactions of various molecules and mechanical characteristics of the system such as
cell membrane, the cytoskeleton, and adhesion to substrate determines the motile
behavior of crawling cells. In the following sections, we'll give a brief introduction
to these important aspects of actin-based motility in lamellipodia.

4.2 Chemical Feedbacks Regulate Actin Mesh Growth

4.2.1 Elongation vs. Nucleation of Actin Filaments

Monomeric actin is the building block of filaments and its availability is key to
the efficient elongation of filaments; moreover, actin is also a key component in
Arp2/3-mediated nucleation process, in which the nucleation of a new filament on
an existing filament requires both an activated Arp2/3 and a G-actin molecule [ 86 ].
Thus, it is essential to understand the interplay between elongation and nucleation
processes. In cells, actin is one of the most abundant proteins, and its availability
facilitates both the speed of protrusion and the rate of nucleation. However, if the
concentration of actin were kept constant, and the concentration of Arp2/3 were
varied, it turns out that the rate of filament nucleation changes monotonically,
but there exists an optimal Arp2/3 concentration at which the protrusion speed is
maximal [ 35 ]. Arp2/3 facilitates the nucleation process, which to a large extent
determines the density of leading edge filaments. On the one hand, at low Arp2/3