cell news 2/2013
33
physics of cancer
the paths of migrating cells
paolo Maiuri
1
, Mael leberre
1
, Matthieu piel
1
, franziska lautenschläger
1,2
1: institut curie, uMr144, 74005, paris, france
2: universität des saarlandes, fakultät 7, 66123, saarbrücken, germany
In order to look at dynamic events in life e.g. directed or un-
directed movements of objects, such as the orbit of a satellite,
the diffusion of molecules, or the path of foraging animals, one
needs to visualize a development in time and space in one frame.
This is done by recording the coordinates of the object and su-
perimposing them on the same background. The connection of
those points is called a trajectory and is often used to retrieve
information about moving objects. A well known everyday ex-
ample would be a map of bus stops. We do not only see on one
page where the bus is going to stop, but we can also use this
bus-trajectory to calculate the bus speed, to see if it’s reaching a
certain place in the most straightforward way and we can even
use this information to predict the position of the bus at a precise
time. By analyzing trajectories we do not only get information
about the instantaneous or mean speed of an object, but also
about the directionality of the path, for example how much the
object is turning during a certain time-window or for how long
it is moving in the same direction. This information is descri-
bed by the persistence of an object and defnes if the object is
moving in a directed motion or rather in a random path. Even a
dynamic evolution within the trajectory – for example an object
moving at different speeds in different stages – can be identifed,
theoretically described, predicted and probably being interfered
with. Such analysis are not only used for buses but are found in
all areas of our daily life, such as tracking population, money or
recently you can even download apps for your smartphone to see
the phone trajectory when it’s getting stolen!
Likewise, the position of living cells can be recorded during cell
migration and cell trajectories can be drawn. This in generally
is done to investigate fundamental migration properties and to
compare the migration behavior of different cell types, for ex-
ample in wound healing essays (Payne, Bhalla et al. 2011) or in
the study of cancer.
The frst reports about trajectories of cells are from the 1970s,
where researchers started to track axons in the brain (Stirling
1978), or analyzed the trajectories of the slime-mold amoebae
and granulocytes with and without chemo tactical cues (Mato,
Losada et al. 1975; Hall 1977; Hall and Peterson 1979). Cell tra-
jectories are generally the way to describe the migration of cells,
allowing to compute their speed or their persistence. There are
several types of migration, cathegorized by cells which do need
adhesion for migration (mesenchymal migration) or cells which
move with no or very low adhesion. This migration type was frst
found in amoebae and was therefore called amoeboid migration
(Friedl and Weigelin 2008; Lämmermann and Sixt 2009; Guck,
Lautenschlager et al. 2010). Those two migration modes are very
different and can be – besides other factors – characterized by
their cellular trajectories. However, cells do not necessarily be-
long to one or the other group of migration and can – by chan-
ging their chemical or physical environment – switch between
those two migration modes (Bergert, Chandradoss et al. 2012).
The change of the physical environment can actually bring cells,
which would not move otherwise, become very motile. This is
the case for dendritic cells of the immune system, which only
start to migrate when they are in a confned environment, wi-
thout the need of integrin adhesion (Faure-Andre, Vargas et al.
2008; Friedl and Weigelin 2008; Lammermann, Bader et al. 2008;
Heuze, Collin et al. 2011). Dendritic cells in confnement move
in an amoeboid manner and have already been studied in dif-
ferent environments such as gels or one dimensional channels,
or tissues (Faure-Andre, Vargas et al. 2008; Lammermann, Bader
et al. 2008). However, the migration of cells in collagen gels is
very hard to control and diffcult to image and cells in channels
only offer one dimensional data. Therefore, we developed a new
system in order to confne cells in a two dimensional way. In our
arrangement we can very precisely defne the height of a roof on
top of the migrating cells, which we generally tune to be between
3 and 10 um. We also modifed our setup in order to have large
felds of view of migrating cells which we can observe over a long
period of time (up to 48 hours) and study long trajectories of the-
se cells. In addition to questions generally asked in migration as-
says such as the speed and persistence of cells, we are interested
in a very specifc information of trajectories: the search behavior
of dendritic cells. Why do we expect dendritic cells to search for
something? The main task of these cells migrating throughout
the body is to uptake possible threats, such as viruses, bacteria
