Computer Simulations of Mechano-Chemical Networks Choreographing Actin Dynamics in Cell Motility - Computational Modeling of Biological Systems - page 250

that the movement of cells is usually robust yet adaptive—cells can respond to
the environmental changes efficiently. With the insights obtained from the analysis
on how a group of chemical species with opposing action regulate the protrusion
dynamics of the model motility system, we can better understand how cells can
finely tune the microscopic polymerization process to achieve certain dynamical
behaviors.

4.2.3 Transport of Molecules

Molecular processes in cell motility are controlled by the reaction-diffusion of
various molecules, thus effective transport of molecules plays an important role in
regulating protrusion dynamics.
The rear part of the lamellipodium of the cell is coupled to the lamellum
(cell body), which serves as a reservoir for molecules. This can be modeled
by coupling the rear part of the lamellipodia to a bulk reservoir of various
molecules, whose concentrations are all kept fixed. This coupling is analogous to
imposing a boundary condition in deterministic reaction-diffusion equations. Actin
monomers are consumed and recycled through the treadmilling process, resulting
in a concentration gradient from the bulk region to the leading edge; the nucleation
of filaments occurs within the activation zone of the membrane, also leading to a
concentration gradient for Arp2/3 molecule from the bulk to the membrane [ 35 ].
From the profiles of concentration gradients, one can derive the local concentrations
of Arp2/3 and actin in the region close to the membrane, where it is of central
importance since it is the location where nucleations occur and also is the main
location for polymerizations. With this, we can analyze what limits the growth
of lamellipodial network [ 35 ]. For example, when actin monomers are abundant,
this favors faster nucleation and tends to deplete Arp2/3, whose bulk concentration
is assumed to be constant and low in absolute value (

100 nM). In such case,
nucleation is limited by the availability of Arp2/3, and the filamentous network
would be sparse. In a sparse filamentous network, there are not enough filaments to
push the membrane, and hence, the protrusion speed would be adversely affected.
As in the filopodial transport discussed above, the abundance of proteins in the cell
body does not necessarily indicate that there would be no problem with protein's
availability at cell's leading edge: if the protein is actively consumed, it needs to be
continuously transported, hence, significant local depletion may still result due to
potential transport bottlenecks [ 35 ].

4.3 Mechanical Aspects of Lamellipodial Protrusion

4.3.1 Cell Membrane

The cytoskeleton of eukaryotic cells is enclosed by the cell membrane. Cell
migration relies on the force generated from polymerizing actin filaments to push