Biomedical Engineering Reference
In-Depth Information
ues to protrude forward activates stress-activated calcium channels, resulting
in transient increases in intracellular calcium concentration. These calcium
transients are postulated to further activate actin-myosin contractility and al-
low the cell to detach. While calcium transients can be observed in smoothly
moving cells, their importance for steady state motility is unclear because
inhibition of calcium transients with intracellular calcium chelators does not
have a significant effect on moving cells (G. Allen, unpublished observations).
It is interesting in this context to compare actin-based motility to the
mechanistically similar, but biochemically distinct, crawling of the nematode
sperm cell [85, 86]. There, motility is driven by assembly and disassembly of
non-polar filaments of a protein called major sperm protein (MSP) rather than
actin. As no analogs to the myosin motors are known in this system (moreover
since the MSP filaments are apolar, the existence of analogous directional
motors appears highly unlikely), it is thought that contraction is generated
solely through disassembly of MSP filaments [87]. Thus, in this system, both
protrusion and contraction forces are generated by assembly and disassembly
of filaments without the action of any myosin-like molecular motors. Even
though the basis for the spatial segregation of MSP filament assembly and
disassembly in the nematode sperm is not entirely clear, this system shows
that, at least in principle, myosin-based contraction need not be essential for
cell motility.
2.3 The Cell Membrane
The cell membrane has several important roles in cell motility. First, because
actin is constantly pushing from within, the cell membrane is stretched lead-
ing to membrane tension that exerts an inward force perpendicular to the cell
surface. In particular, this force will act on the barbed ends of actin filaments
at the leading edge, retarding their growth. Experiments using pharmacolog-
ical agents to perturb physical properties of the cell membrane in fibroblasts
and endothelial cells have implicated membrane tension or membrane mi-
croviscosity as possible factors limiting the speed of cell migration [88, 89].
Second, the cell membrane plays a crucial role in regulating the intracellular
environment and cell volume through the action of various channels in the cell
membrane, including ion channels and aquaporins (reviewed in [90]). Finally,
the cell membrane serves to localize various proteins and lipids that have im-
portant roles in adhesion, regulation of actin dynamics, and coordination of
signaling information (reviewed in [8]).
The lamellipodium of moving cells in general, and keratocytes in partic-
ular, is very thin
∼
200nm (see Figure 2.2; References [42, 91]) compared to
the cell body (5
10
μ
m). This thin structure is maintained by restricting
protrusion to the apex of the leading edge. The mechanisms responsible for
generating and maintaining this unique dynamic interface between the mem-
brane and the cytoskeleton at the leading edge are entirely unclear, but most
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