Biomedical Engineering Reference
In-Depth Information
force. We obtained the force and velocity relationship for
M. mobile
gliding
(see Figure 6.13B) and found that i)
M. mobile
can continuously change speed,
responding to loads at various speeds of flow, suggesting that the gliding can
respond to a wide variety of loads, as may occur in mucous on the surface of
host tissues; ii) the maximal (stall) force was 27 piconewtons (pN), or roughly
1,800 times the force [15 femtonewtons (fN)] required to thrust a
Mycoplasma
cell [64, 65]; and iii) the maximal force did not depend on the temperature
but the speed did, suggesting that force generation and stroke are different
steps.
The number of Gli349 molecules on the cell surface was quantified by
titrating the antibody binding to the cell surface [27]. We estimated that there
are around 450 Gli349 molecules on a cell. Assuming that a quarter of them
are involved in gliding at any given moment and participate in generating the
maximal force detected, the force exerted through each leg would be 0.24 pN,
which is much smaller than the value of conventional motor proteins [66, 67].
6.3.14 Features of Mechanism and Centipede Model
The mechanism may depend on repeated binding based on energy from ATP.
It has these features in common with conventional motor proteins such as
myosin and kinesin. However,
Mycoplasma
gliding has the following unique
features: i) the machinery is half exposed; ii) the ATPase and binding site are
positioned about 50nm apart; iii) the “rail”, fixed sialic acid, has no polarity;
iv) the stall force is as small as 0.24pN per unit, if we assume that one-quarter
of all gliding units are engaged at any moment; and v) the mechanism probably
does not have a pushing step because the longest rod of the Gli349 molecule
is flexible.
Considering these features and other results obtained so far, we suggest a
“centipede (power stroke) model”, a working model to explain the mechanism
[68, 5, 48, 27]. There, each gliding unit is in a mechanical cycle, which is
composed of a series of states [(a-f) in Figure 6.14] and transition steps: i)
stroke, ii) movement, iii) release, iv) return, v) initial binding, and vi) tight
binding. The major assumption here is that the tension exerted to the leg
causes a progression of steps, as indicated by the lightning dashes in the figure.
In Stage (a), the leg (Gli349) tightly binds to sialic acid on the solid surface.
The force exerted to the leg triggers a conformational change in the upper part
of the leg, causing the stroke (i). This trigger is assumed. The unit is waiting
for a new molecule of ATP at Stage (a), because the ghosts stop gliding when
ATP is depleted from permeabilization by triton. At Stage (b), higher tension
is exerted to the leg and actual movement (ii) occurs. Considering that the
leg length about 50nm, and the gliding speed is 2.5 microns per second, this
step should occur within 10ms at the slowest. The stall by mechanical force
should occur at this step. At Stage (c), tension applied to the leg decreases
and this change triggers the leg to release sialic acid at step (iii). The decrease
in tension also causes return (iv) of the upper part of the leg to the initial
