A fine balance among key biophysical factors is required for recovery of bipolar mitotic spindle from monopolar and multipolar abnormalities.
Mol Biol Cell
; 34(9): ar90, 2023 08 01.
Article
em En
| MEDLINE
| ID: mdl-37342878
ABSTRACT
During mitosis, equal partitioning of chromosomes into two daughter cells requires assembly of a bipolar mitotic spindle. Because the spindle poles are each organized by a centrosome in animal cells, centrosome defects can lead to monopolar or multipolar spindles. However, the cell can effectively recover the bipolar spindle by separating the centrosomes in monopolar spindles and clustering them in multipolar spindles. To interrogate how a cell can separate and cluster centrosomes as needed to form a bipolar spindle, we developed a biophysical model, based on experimental data, which uses effective potential energies to describe key mechanical forces driving centrosome movements during spindle assembly. Our model identified general biophysical factors crucial for robust bipolarization of spindles that start as monopolar or multipolar. These factors include appropriate force fluctuation between centrosomes, balance between repulsive and attractive forces between centrosomes, exclusion of the centrosomes from the cell center, proper cell size and geometry, and a limited centrosome number. Consistently, we found experimentally that bipolar centrosome clustering is promoted as mitotic cell aspect ratio and volume decrease in tetraploid cancer cells. Our model provides mechanistic explanations for many more experimental phenomena and a useful theoretical framework for future studies of spindle assembly.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Centrossomo
/
Fuso Acromático
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article