Mechanistic three-dimensional model to study centrosome positioning in the interphase cell.

Abstract

During the interphase in mammalian cells, the position of the centrosome is actively maintained at a small but finite distance away from the nucleus. The perinuclear positioning of the centrosome is crucial for cellular trafficking and progression into mitosis. Although the literature suggests that the contributions of the microtubule-associated forces bring the centrosome to the center of the cell, the position of the centrosome was merely investigated in the absence of the nucleus. Upon performing a coarse-grained simulation study with mathematical analysis, we show that the combined effect of the forces due to the cell cortex and the nucleus facilitate the centrosome positioning. Our study also demonstrates that in the absence of nucleus-based forces, the centrosome collapses on the nucleus due to cortical forces. Depending upon the magnitudes of the cortical forces and the nucleus-based forces, the centrosome appears to stay at various distances away from the nucleus. Such null force regions are found to be stable as well as unstable fixed points. This study uncovers a set of redundant schemes that the cell may adopt to produce the required cortical and nucleus-based forces stabilizing the centrosome at a finite distance away from the nucleus.