Microtubule Forces and Organization - Cell Motility - page 93

4
Microtubule Forces and Organization
Marileen Dogterom, Julien Husson, Liedewij Laan, Laura Munteanu, and
Christian Tischer
FOM Institute for Atomic and Molecular Physics (AMOLF), Kruislaan 407, 1098
SJ Amsterdam, The Netherlands. Tel: [phone], [e-mail]
4.1 Introduction
Eukaryotic cells contain a network of semi-flexible protein polymers that pro-
vide the cell with a mechanical framework for the control of cell shape, cell
locomotion as well as intracellular transport, and the spatial organization of
intracellular organelles [1]. Microtubules are the stiffest component of this
so-called cytoskeleton. They consist of hollow tubes that are 25 nm wide
and typically built from 13 protofilaments of tubulin protein dimers [2]. The
way microtubules are spatially organized in the cell depends strongly on the
cell type and its cell cycle state (see Figure 4.1). For example, in a typical
animal cell that is in interphase (i.e., not dividing) the microtubules are nu-
cleated by a single centrosome, which acts as microtubule organizing center
(MTOC) close to the cell nucleus. From this organizing center, stiff dynamic
microtubules radiate with their fast growing plus end towards the periphery
of the cell. This particular microtubule organization serves several purposes:
motor proteins such as kinesin and dynein follow the orientation of the micro-
tubules and transport cargo either towards the plus end of the microtubules
(the cell periphery) or the minus end of the microtubules (the cell interior).
During mitosis, microtubules are drastically reorganized to form the mitotic
spindle. In this configuration dynamic microtubules are responsible for faith-
fully dividing the duplicated chromosomes between the two newly forming
daughter cells, first by positioning duplicated chromosome pairs in the mid-
dle of the cell and then by pulling exactly half of the chromosomes to each
cell pole. Dynamic microtubule ends also interact with the cell cortex, where
they can, for example, respond to external cues and help polarize a motile
cell into a particular direction. For many of the cellular functions of micro-
tubules, it is essential that their dynamic properties are precisely controlled.
Microtubules constantly switch between growing and shrinking states, through
events termed catastrophes and rescues (this process is called dynamic insta-
bility). Control of these switching events allows the cell to locally control the