Biomechanics of chromosome alignment at the spindle midplane

Abstract

During metaphase, chromosomes are aligned in a lineup at the equatorial plane of the spindle to ensure synchronous poleward movement of chromatids in anaphase and proper nuclear reformation at the end of mitosis. Chromosome alignment relies on microtubules, several types of motor protein and numerous other microtubule-associated and regulatory proteins. Because of the multitude of players involved, the mechanisms of chromosome alignment are still under debate. Here, we discuss the current models of alignment based on poleward pulling forces exerted onto sister kinetochores by kinetochore microtubules, which show length-dependent dynamics and undergo poleward flux, and polar ejection forces that push the chromosome arms away from the pole. We link these models with the recent ideas based on mechanical coupling between bridging and kinetochore microtubules, where sliding of bridging microtubules promotes overlap length-dependent sliding of kinetochore fibers and thus the alignment of sister kinetochores at the spindle equator. Finally, we discuss theoretical models of forces acting on chromosomes during metaphase. ll

The chirality of the mitotic spindle provides a mechanical response to forces and depends on microtubule motors and augmin

“… 5 The forces in the spindle are crucial for proper spindle functioning in each phase of mitosis. Kinetochore fibers exert forces necessary for the positioning of the chromosomes at the center of the spindle in metaphase 6 , 7 , 8 and for pulling the chromosomes apart during anaphase. 9 , 10 , 11 On the other hand, overlap bundles balance the forces at kinetochores by acting as bridges between sister kinetochore fibers in metaphase and anaphase 12 , 13 , 14 , 15 and also regulate pole separation in anaphase.…”

The chirality of the mitotic spindle provides a mechanical response to forces and depends on microtubule motors and augmin

“…Forces in the spindle are crucial for proper spindle functioning in each phase of mitosis. Kinetochore fibers exert forces necessary for the positioning of the chromosomes at the center of the spindle in metaphase [6][7][8] and for pulling the chromosomes apart during anaphase [9][10][11] . On the other hand, overlap bundles balance the forces at kinetochores by acting as bridges between sister kinetochore fibers in metaphase and anaphase [12][13][14][15] , and also regulate pole separation in anaphase [16][17][18] .…”

Highway to hell‐thy meiotic divisions: Chromosome passenger complex functions driven by microtubules

“…These have been termed "bridging fibers," [116,117] contain several motor proteins that can regulate microtubule overlaps, [118] and have been proposed to use length-dependent forces to align chromosomes. [118,119] Whether these are enriched for the CPC, as expected because they contain anti-parallel microtubule overlaps, and how they transmit forces to the kinetochores and regulate attachments is not clear. Bridging fibers are intriguing structures, however, because they could link kinetochores of homologous chromosomes in meiosis I with antiparallel microtubules (Figure 3).…”