Deciphering the biomechanical origins of microtubule aster decentering

Asters are radiating arrays of microtubules (MTs) associated with the centrosome organelle in dividing eukaryotic cells. These cytoskeletal structures play a critical role in the positioning and orientation of the mitotic spindle, pronuclear migration, and cell homeostasis. Recent experimental and theoretical studies have shown that centrosome centration is primarily governed by cortical pulling forces. To gain new insight into centrosome behavior, in vitro experiments have been conducted using droplets of Xenopus laevis cycling extract seeded with artificial centrosomes that nucleate microtubules to form asters. These experiments reveal that centrosome centering in each cycle is consistently followed by an abrupt decentering. Remarkably, this decentering exhibits a characteristic timescale that is reproducible across all droplets. In contrast to centration, the physical mechanisms responsible for centrosome decentering have received little attention and remain poorly understood. To uncover the biomechanical origins of this intriguing phenomenon, we develop a biophysical model that captures key features of aster dynamics and test several hypotheses that could give rise to aster decentering. We model the aster as a dense bed of thin, flexible, yet inextensible fibers, along which molecular motors can walk and exert forces. This fiber bed is anchored to a rigid spherical core (representing the centrosome), immersed in cytoplasm modeled as a linear Stokes fluid, and confined within a spherical droplet, closely replicating the experimental setup. For each alternative mechanical pathway that can lead to decentering, we construct phase diagrams to investigate the influence of fiber density, fiber branching, and confinement. Finally, through comparisons with experiments and simple dimensional analysis, we assess which mechanisms are the most likely candidates for explaining the observed centrosome motion.