Biomedical Engineering Reference
In-Depth Information
velocity in a way that is similar to the effect of a reduction in tubulin concen-
tration, namely by reducing the rate of tubulin addition. This is consistent
with what is predicted by the Brownian ratchet model.
The finding that forces generated by growing microtubules in contact with
a barrier increase the catastrophe rate hints at another mechanism (besides
the action of microtubule associated proteins) by which cells may locally reg-
ulate microtubule dynamics. Depending on the geometry and size of the cell,
microtubules should experience compressive forces when they run into the cell
boundary that may prevent microtubules from growing longer than they need
to be. Indeed, in several cell types it has been observed that microtubule catas-
trophe rates are specifically enhanced near or at the cell boundary [4, 29, 30].
Whether these effects are due (in part) to force effects remains to be investi-
gated, although we found compelling evidence that in small fission yeast cells,
this is indeed the case (see next Section).
4.5 Microtubule Forces in Fission Yeast Cells
In interphase fission yeast cells, microtubule pushing forces have a clear func-
tional role to play. To keep the position of the nucleus near the middle of the
cell, microtubules nucleated at the nuclear membrane grow towards the cell
ends where they push against the cell membrane for a short time before un-
dergoing a catastrophe and shrinking back to their nucleation site [4]. During
this contact time, growth of the microtubules can be correlated with deforma-
tion of the nuclear membrane, as well as motion of the complete nucleus away
from the cell end. For the correct positioning of the nucleus in this system,
it is not only important that forces are generated, but also that microtubules
undergo catastrophes some time after they reach the cell end. In the absence
of sucient catastrophes, microtubules that continue to grow eventually curl
around the cell ends, which compromises their ability to position the nucleus
correctly. One option for the cell, to ensure that catastrophes occur when mi-
crotubules reach the cell ends, is to target a protein factor to the cell ends that
can locally enhance the rate of catastrophes. Indeed, it is known that in this
system proteins that travel at the ends of microtubules accumulate near the
cell ends where they could perform such a local role (see Figure 4.3). Alter-
natively, it is possible that compressive forces generated when microtubules
polymerize against the cell end have the same catastrophe-enhancing effect
that was observed
in vitro
.
Evidence for such a force effect comes from the quantitative analysis of
catastrophe rates as a function of position in the cell. If force has an effect
on the catastrophe rate one would expect to find an increase in catastrophes
specifically at the cell ends that is correlated with the generation of force. In
Figure 4.7, we show an example where near-simultaneous catastrophes occur
on microtubules in a bundle that make contact with both cell ends simulta-
neously. In this situation, a maximum compressive force is generated because
