cell news 2/2013
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or other pathogens and to alert the immune system. However, to
take something up, it needs to be found frst. Here fnding means
two things: the physical encounter, and then the uptake by the
dendritic cell. So do dendritic cells really search for pathogens
or does this happen in a rather random manner? We are loo-
king into the trajectories of dendritic cells in order to understand
their behavior and to compare it to theoretical models. Different
models exist which all describe search behavior. However, they
differ in their parameters and therefore settings of the system.
For example, if a searcher is trying to fnd random objects which
do disappear forever once he found them, then he might just have
the most success by walking straight and picking them up on his
way. However, such a strategy might not be the most successful
if the object can reappear after it was found once, in which case
so called levy walks might be better (Viswanathan, Buldyrev et al.
1999; Bartumeus, Catalan et al. 2002; James, Plank et al. 2008).
But if targets are not randomly but instead regularly distributed,
another theory describes an optimized search strategy, which is
a simple persistent random walk (Tejedor, Voituriez et al. 2012).
However, for some searchers there is a specifc diffculty: they
cannot move and ‘fnd’ at the same time. In daily life this might
be best illustrated by a person having lost its key on a sandy
beach: in order to cover some area the person needs to move,
but since the key might be well hidden in the sand, he also needs
to stop moving, kneel down and actually look for the key. Such
biphasic search behavior is described in intermittent search stra-
tegies (Benichou, Loverdo et al. 2006; Benichou, Loverdo et al.
2011). The fast moving phases of the searcher in this theory are
described as persistent, the so called ballistic phases and the time
while the searcher is staying in one area to take up objects by a
random, the so called diffusive movement. We use single cell tra-
jectories to investigate which way dendritic cells are migrating in
order to sample their environment best. Since dendritic cells have
been shown in 1D microchannels to show a biphasic migration
behavior (Faure-Andre, Vargas et al. 2008), they might indeed use
an intermittent search strategy in order to look for pathogens.
To investigate this question, we analyze our 2D cell trajectories
not only in a conventional way, but we also look out for different
modes of migration within one cellular migration track (fast and
persistent parts versus slower and diffusive parts). An example
of such an intermittent migration track is given in Figure 1. The
distinction between different modes is done by analysis of the
means square displacement of the trajectories. A comparison of
our data with theoretical models will enable us to fnd out if
cells are searching and if they do, which search strategy they are
using? If cells do indeed have a specifc strategy it will be inte-
resting to see if this is adapted and optimized for certain types
of environments.
References:
Bartumeus, F., J. Catalan, et al. (2002). "Optimizing the encounter rate in biological interac-
tions: Levy versus Brownian strategies." Phys Rev Lett 88(9): 12.
Benichou, O., C. Loverdo, et al. (2006). "Two-dimensional intermittent search processes: An
alternative to Levy fight strategies." Physical Review E 74(2): 020102.
Benichou, O., C. Loverdo, et al. (2011). "Intermittent search strategies." Reviews of Modern
Physics 83(1): 81.
Bergert, M., S. D. Chandradoss, et al. (2012). "Cell mechanics control rapid transitions between
blebs and lamellipodia during migration." Proc Natl Acad Sci U S A 109(36): 14434-14439.
Faure-Andre, G., P. Vargas, et al. (2008). "Regulation of dendritic cell migration by CD74, the
MHC class II-associated invariant chain." Science 322(5908): 1705-1710.
Friedl, P. and B. Weigelin (2008). "Interstitial leukocyte migration and immune function." Nat
Immunol 9(9): 960-969.
Guck, J., F. Lautenschlager, et al. (2010). "Critical review: cellular mechanobiology and amoe-
Figure 3:
Example of intermittent migration trajectory over a time course of 15h. Left: Overlay of phase contrast images of migrating dendritic cell. Scale bar 50 um.
Right: Trajectory of the same dendritic cell where persistent (red) and diffusive (black) migration modes have been identifed.
physics of cancer
