Biomedical Engineering Reference
In-Depth Information
signal near the leading edge attributed to dilution by incoming water there
[103]. Note that such water influx at the leading edge would also reduce the
concentration of proteins such as actin monomers required for assembly of the
actin meshwork.
Alternatively, it has been implied that intracellular fluid flow toward the
leading edge (see Figure 2.9c) might contribute to motility by expediting
transport of actin and other soluble proteins to the leading edge. Forward
transport of actin into protruding regions at a speed of more than 5
μ
m
/
s
was measured by fluorescence localization after photobleaching of GFP-tagged
β
-actin in fibroblasts [104]. While the results excluded simple diffusion as
the sole transport mechanism, and pointed to the existence of some form
of active transport, its nature was not determined. The authors suggested
that directed transport could be driven by forward hydrodynamic flow with
a magnitude of several
μ
m
/
s generated by myosin contraction at the cell rear
that they postulated “squeezed” fluid forward. Our own observations in fish
keratocytes that move more than an order of magnitude faster than fibroblasts
show that such rapid forward flows do not exist in keratocytes (K. Keren et
al., unpublished observations). Intracellular fluid flow of a smaller magnitude
that assists recycling of monomeric actin to the leading edge was predicted in
a multiscale 2D computational model of the lamellipodium [23]. However, the
relative importance of this fluid flow for recycling was small and the model
showed that diffusion should be sucient for recycling monomeric actin back
to the leading edge even, in rapidly moving cells such as keratocytes.
We have described several schemes for the pattern of fluid flow in moving
cells (summarized in Figure 2.9). All possible scenarios imply a relative veloc-
ity between the cytosolic fluid and the actin network. However, the various
models assign very different roles for fluid flow. Fluid flow is projected to play
an active role in promoting motility by either relieving membrane tension al-
beit at the price of reducing protein concentration at the leading edge (see
Figure 2.9b), or by increasing protein concentration at the leading edge (see
Figure 2.9c). Alternatively in the passive model (see Figure 2.9a) fluid moves
along inactively with the cell. These mutually excluding scenarios are each
supported by several indirect results. However, direct measurements of fluid
flow in moving cells, which would resolve the controversy, are lacking due to
the diculty of measuring relatively small flows of fluid that interpenetrates a
dense meshwork characterized by a typical pore size of
30-50nm (see Figure
2.3). Thus, the important question of how the fluid is behaving in a mov-
ing cell, and what role fluid dynamics plays in cell motility, remains for now
unanswered.
∼
2.5 Feedback Mechanisms and Large-Scale Integration
Although for the sake of simplicity the sub-processes involved in cell motility
(namely, protrusion, contraction, retraction and adhesion) are often treated in-
