Systems Biomechanics of the Cell - Systems Biomechanics of the Cell - page 41

Fig. 24 Dynamics of the centrosome orientation in a lymphocyte developing sequentially two
immunological synapses. Insets show the model cell, nucleus, centrosome, microtubules, and cell
contact areas. Two alternative simulations differing in the position of the second synapse follow
the simulation with the first synapse. Reproduced from Kim and Maly ( 2009 ) under the Creative
Commons Attribution License
reorientation movement (the side next to which the synapse initially developed), a
relatively tight “bundle” of microtubules is formed, which is separated from the
microtubules that were trailing by a distinctive gap.
It can be observed parenthetically that “bundling” of microtubules is frequently
seen also in the energy-minimization model discussed in the last section. They arise
from multiple microtubules adopting similar conformations that are favored by
bending in the confined intracellular space. Assumption of “cross-linking” that is
common among the interpretations of microtubule bundling as observed in experi-
ments has an obvious simpler alternative in the light of these calculations. Returning
to the lymphocyte simulation, the predicted gap between the leading “bundle” and
the trailing microtubules is indeed visible in a three-dimensional experimental
image of an early T cell-target cell conjugate (figure 6a in Kuhn and Poenie 2002 ).
The strong asymmetry thus induced in the aster by the active sliding appears to
be responsible for the ratchet-like behavior of the microtubule cytoskeleton, which
is predicted by the Kim-Maly model when the T cell develops a second synapse.
The centrosome readily reorients by another 90° in the same direction as it did the
first time, but does not reorient in the opposite direction (Fig. 24 ). This easily test-
able prediction implies that the systems biomechanics of the cell body imposes
specific constraints on the functionality of the cytotoxic lymphocytes during the
immune response. More broadly, the emergent irreversibility arising from con-
straining of the cell body by the cell boundary deserves a detailed theoretical inves-
tigation in the context of various cell-biological phenomena and must be taken into
account when designing and interpreting experiments.