Centrosome Centering and Decentering by Microtubule Network Rearrangement

Abstract

The centrosome is positioned at the cell center by pushing and pulling forces transmitted by microtubules (MTs). Centrosome decentering is often considered to result from asymmetric, cortical pulling forces exerted in particular by molecular motors on MTs and controlled by external cues affecting the cell cortex locally. Here we used numerical simulations to investigate the possibility that it could equally result from the redistribution of pushing forces due to a reorientation of MTs. We first showed that MT gliding along cell edges and pivoting around the centrosome regulate MT rearrangement and thereby direct the spatial distribution of pushing forces, whereas the number, dynamics, and stiffness of MTs determine the magnitude of these forces. By modulating these parameters, we identified different regimes, involving both pushing and pulling forces, characterized by robust centrosome centering, robust off-centering, or "reactive" positioning. In the last-named conditions, weak asymmetric cues can induce a misbalance of pushing and pulling forces, resulting in an abrupt transition from a centered to an off-centered position. Taken together, these results point to the central role played by the configuration of the MTs on the distribution of pushing forces that position the centrosome. We suggest that asymmetric external cues should not be seen as direct driver of centrosome decentering and cell polarization but instead as inducers of an effective reorganization of the MT network, fostering centrosome motion to the cell periphery.

Matrix rigidity regulates microtubule network polarization in migration

“…Cell height and spreading might also require further investigation. The reason for the central location of the MTOC could be explained by microtubule ends pushing the cell boundary, thereby forcing a centralized location of MTOC when cells are immobilized on patterns, matching the work of others in vitro on MT polymerization forces [Letort et al, ]. Collectively, these results demonstrate that cytoskeletal polarity depends on matrix stiffness and that there is an additional dependence on cell migration for polarity of the MTOC which is not required for MIIB polarity.…”

Dynein self-organizes while translocating the centrosome in T-cells

“…First anchoring stiffness 500 pN/µm Rotational stiffness on the MTs at the center of the centrosome, as proposed previously (Letort et al, 2016).…”

“…The number of MTs has been estimated from previous experimental data (Hooikaas et al, 2020) Each MT has two Hookean spring stiffnesses that force the centrosome into an aster-like conformation. The first stiffness is located at the centrosome center, while the second connects a single point on the centrosome surface to the MT (Letort et al, 2016). This second link enforces a radial aster-like conformation.…”

“…We use a classical two-state model to describe the growth and shrinkage of MTs, as implemented in Cytosim and used for previous studies (Dogterom and Yurke, 1997;Janson et al, 2003;Letort et al, 2016;Lacroix et al, 2018). This model includes force-dependent MT growth and catastrophe.…”

Actin filaments regulate microtubule growth at the centrosome

“…Interestingly, the increase in microtubules may contribute to B‐cell polarization, a hallmark of their activation (Yuseff et al , ), by promoting centrosome off‐centring. Indeed, a high quantity of microtubules can break network symmetry and force centrosome off‐centring and its displacement to the cell periphery through the reorientation of pushing forces produced at the centrosome by microtubule growth (Letort et al , ; Burute et al , ; Pitaval et al , ). Therefore, centrosomal actin filament disassembly could be involved both in the disengagement of the centrosome from the nucleus (Obino et al , ) and in the stimulation and reorganization of microtubule‐based pushing forces to drive centrosome motion towards the cell periphery.…”