Systems Biomechanics of the Cell - Systems Biomechanics of the Cell - page 3

asymmetry of the microtubule aster in some situations, or maintenance of its
symmetry within the cell outline in others, has been a subject of experimental inves-
tigation (Kupfer et al. 1982 ; Euteneuer and Schliwa 1992 ; Koonce et al. 1999 ; Piel
et al. 2000 ; Etienne-Manneville and Hall 2001 ; Yvon et al. 2002 ; Burakov et al.
2003 ; Gomes et al. 2005 ; Dupin et al. 2009 ).
In the compact immune cells, such as the lymphocytes, which have nearly spher-
ical cell bodies, the eccentric position of the centrosome appears to be constitutive,
and only its orientation to a specific side of the cell is regulated by the antigen-
mediated cell-cell interaction. In the thinly spread epithelioid cells of the wound-
closure experiments, which with the exception of the nucleus are nearly flat, the
centrality and eccentricity of the centrosome were initially a matter of debate. It is
now generally accepted that although the centrosome in these cells may not be cen-
tered with respect to the nucleus, it is centered with respect to the cell outline. The
terminology adopted here makes this observation clearer: Although the orientation
of the cell body may differ, it is centered in the cell boundary. The apparent funda-
mental difference between the centrosome positioning in flat and spherical cells
would require explanation and might serve as a test of our understanding of the
centrosome positioning mechanisms; however, the quantitative analysis reviewed
below casts doubt on this interpretation of the experimental results. Irrespectively,
positioning of the cell body and especially of the centrosome as its best-defined
structural and functional marker within the cell boundary is of central importance in
the biology of the cell.
The mechanism of the positioning is not well understood. It is unclear how gen-
eral the mechanisms are that have been implicated, or how exactly they interact or
interfere in each cell type and in each individual cell. Among the experimentally
implicated mechanisms there are microtubule dynamics (Stowers et al. 1995 ;
Lowin-Kropf et al. 1998 ; Faivre-Moskalenko and Dogterom 2002 ; Yvon et al.
2002 ; Burakov et al. 2003 ), action of cortically anchored molecular motors of the
dynein type (Etienne-Manneville and Hall 2001 ; Burakov et al. 2003 ; Levy and
Holzbaur 2008 ), movement of the entire cell body that entrains the centrosome
(Arkhipov and Maly 2006a , 2008 ), flow of cortical actomyosin that entrains micro-
tubules (Burakov et al. 2003 ; Gomes et al. 2005 ), and even cell population-level
kinetic selection linked to the direction of transport along the microtubules
(Arkhipov and Maly 2006b , 2007 ).
In view of the complexity of centrosome positioning and with the goal of pro-
gressing toward a generalized and integrated mechanistic understanding of it, it is
imperative to study systematically the contributions and theoretical capacities of
each contributing mechanism, starting from the first principles. Arguably the sim-
plest of the contributions, and the one which is the most inseparable from the micro-
tubule cytoskeleton itself, is the effect that the bending elasticity of microtubules
must have on the positioning of the centrosome within the cell boundary.
The fundamental role of the elastic compactization of the microtubule cytoskel-
eton within the constraints of the cell boundary for centrosome positioning was
recognized early by Holy. One version of the original theory considered the abso-
lute energy minimum of an aster of a large finite number of evenly spaced