Biomedical Engineering Reference
In-Depth Information
Figure 2.5.
The graded radial extension model. (a) Schematic illustration of a
cell moving forward while maintaining constant shape by graded radial extension.
Protrusion at each point along the leading edge proceeds in a direction locally per-
pendicular to the edge, at a protrusion rate which decreases away from the center.
(b) For comparison, a schematic illustration of a cell moving forward by constant ex-
tension which is everywhere equal in magnitude and direction to the net cell speed.
The gray arrows depict the direction of cell motion.
sory proteins such as Arp2/3 and VASP), and the inherent time required for
actin polymerization. At present, it is not clear which factor is rate limiting
in the protrusion process at the leading edge, and the answer may well be
different depending on the cell type and/or on the specific conditions within
a particular cell.
The local protrusive force generated by the leading edge of moving ker-
atocytes has recently been measured by placing a cantilever in the path of
a protruding lamellipodium [71]. The measured force velocity relationship
displayed a surprising sharp velocity drop upon contact at very small loads
(
<
100pN
/μ
m), the nature of which is unknown. At higher loads, the veloc-
ity was insensitive to load over a broad range of loads until eventually there
was a sharp decrease in velocity and protrusion stalled. The measured stall
force was
∼
1nN, with some variation among different cells, which amounts
4pN force per filament. The force velocity relationship of an
in vitro
dendritic actin meshwork was also found to be insensitive to load force over
a wide range of loads [72]. Interestingly, the force velocity relationship mea-
sured
in vitro
was dependent on the load history, so more than one possible
velocity was observed for a given load. Both results [71, 72] are suggestive of
feedback mechanisms between the mechanical load imposed on a protruding
actin network and the molecular processes responsible for network growth and
organization. Such force-dependent network remodeling may play an impor-
tant role in the ability of moving cells to respond to mechanical variations in
their
in vivo
environment.
Precise control and coordination of local protrusion rates is required to
maintain the coherent leading edge of motile keratocytes (see Figure 2.1). A
phenomenological model which attempts to address this issue is the graded
∼
to
