Agence Nationale pour la Recherche

AAPG2022 – PRC (2022-2026)

SHARP – Sharp Transition in the positioning of the microtubule-organizing center

Differentiated cells are polarized. A common and essential feature of polarized cells is the positioning of the centrosome, the main microtubule organizing center (MTOC), at the periphery of the cell, next to the active organelle (the flagellum of spermatozoa, the axon of neurons, the microvilli of epithelial cells, the immune synapse of lymphocytes). By contrast, in proliferating cells, it is located at the geometric center of the cell, hence its name, centrosome for “center of the soma”. The transition from one state to the other is not progressive. The regulation of the positioning of the MTOC goes from a robust and precise centering process to a total decentering to the periphery of the cell. The absence of intermediate states implies that the positioning mechanism is based on a nonlinear interaction between the forces acting on the microtubule network and the position of the center of this network, which induces a sharp transition in MTOC positioning. This sharp transition gives the cells both robust centering or decentering capabilities over wide ranges of conditions, as well as a highly sensitive state in a reduced window of parameters. The objective of this proposal is to study the physical basis of this complex regulation of the MTOC positioning mechanism by reconstructing in vitro all the key elements ensuring the different types of force production on microtubules, and to couple this experimental study to the establishment of a physical model capable of accounting for both the robust phases and the sharp transition.