Biomedical Engineering Reference
In-Depth Information
1.3
Basic Structural Components of a Migrating Cell
1.3.1
Cytoskeleton
The cytoskeleton is a system of functionally adaptable fi laments that is responsible
for intracellular transport, cell migration and structural support necessary for cell
shape maintenance. In most cell types, it is comprised of three types of fi laments
that are constructed from three different protein families; the actin fi laments
(microfi laments), intermediate fi laments and microtubules.
Although the fi laments of the cytoskeleton have different mechanical properties
and perform different functions within a cell, collectively they determine the cell
mechanical properties. Moreover, other proteins interact with them, enabling a cell
to establish and maintain internal order, to reshape and remodel its surface, to transport
other organelles, and to move itself to another location (Alberts et al.
1994
). By
regulating the structural dynamics and hierarchical organization of these fi laments,
cells are able to build a wide range of sophisticated structures like lamellipodia,
fl agella, and fi lopodia that are used for cell migration.
1.3.1.1
Actin Cytoskeleton
A schematic illustration of a polarized migrating cell showing different structural
components of a migrating cell is shown in Fig.
1.2a
. Actin fi laments are shown
in Fig.
1.2b
interacting with myosin II bipolar fi laments (inset Fig.
1.2b
). Actin
fi laments, also referred to as F-actin, assemble from G-actin (“G” stands for globu-
lar) into long strands consisting of up to 350 amino acids. These fi laments are only
stable when two strands coil around each other to form a double helix string with a
diameter of ~7 nm.
Actin fi laments also interact with other actin-associated intracellular proteins such
as
-actinin, fi lamin, arp2/3 etc. to form a meshwork structure (actin fi lament network).
Because of this, actin fi laments, which are but wobbly stings, are capable of not only
generating suffi cient force for migration but also providing mechanical support neces-
sary for cell shape maintenance. Actin fi laments are considered to be semifl exible
because their characteristic length (~10-17
ʱ
ʼ
m) is comparable to their physiological
contour length (~0.1-10
m) (Chaudhuri et al.
2007
; Gittes et al.
1993
).
An important feature of actin fi laments is that they posses polarity, in the sense
that each end of a fi lament has a different binding affi nity for ATP-bound G-actin.
The fi lament end with a higher binding affi nity for G-actin is known as the plus end
(or barbed end) while the other end with low binding affi nity is known as the minus
end (or pointed end). Filaments elongate when ATP-bound G-actin monomers bind
to the plus end by a process known as polymerization, and shrink when G-actin
dissociate from the minus end by a process known as depolymerization. These two
processes contribute to fi lament treadmilling when they occur at equal rates, and the
balance between the two determines the rate of cell movement. Molecular mechanisms
of these processes are discussed in more detail in the next section.
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