The mitotic spindle is chiral due to torques within microtubule bundles

Abstract

Mitosis relies on forces generated in the spindle, a micro-machine composed of microtubules and associated proteins. Forces are required for the congression of chromosomes to the metaphase plate and their separation in anaphase. However, besides forces, torques may exist in the spindle, yet they have not been investigated. Here we show that the spindle is chiral. Chirality is evident from the finding that microtubule bundles in human spindles follow a left-handed helical path, which cannot be explained by forces but rather by torques. Kinesin-5 (Kif11/Eg5) inactivation abolishes spindle chirality. Our theoretical model predicts that bending and twisting moments may generate curved shapes of bundles. We found that bundles turn by about −2 deg µm−1 around the spindle axis, which we explain by a twisting moment of roughly −10 pNµm. We conclude that torques, in addition to forces, exist in the spindle and determine its chiral architecture.

Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling

“…Computational modeling has been used previously to study the mitotic spindle [3,4,67]. Recent work on spindle and MT organization includes studies of spindle elongation and force balance [59,68], the formation and maintenance of antiparallel MT overlaps [69,70], MT bundling and sliding [15], spindle movements and positioning [71,72], spindle length and shape [15,51,52,73,74], MT organization [75], and spindle assembly from a bipolar initial condition [32,76]. Models of kinetochore-MT attachment and biorientation have examined capture of lost kinetochores [63,77], chromosome reorientation after MT attachment [31], attachment error correction [33,39,78,79], and chromosome movement on the spindle [52,61,[80][81][82].…”

Effect of static magnetic field on DNA synthesis: The interplay between DNA chirality and magnetic field left‐right asymmetry

“…16,17 Chirality can also be observed as the directional rotation of cellular organelles, cytoskeleton, and cells as a whole. 18 Findings [19][20][21][22][23] suggest that chirality is a fundamental property of the cell that depends on the chiral nature of the mitotic spindle and cytoskeleton network, such as actin and microtubule bundles. It is believed that all amino acids are present in all proteins only in the left configuration.…”

Topological states in chiral active matter: Dynamic blue phases and active half-skyrmions

“…In nature, chirality is ubiquitous, ranging from the helical structure of DNA 16 and bacterial flagella 17 to numerous biopolymers such as actin, chitin and microtubules 18 . On a more macroscopic level, the mitotic spindle is chiral due to torques within microtubule bundles 19 , cells can develop chiral actomyosin patterns 20 , and there is even tissue-scale chirality in spontaneous cellular shear flow 21 . Motivated by this common occurrence of chirality in biological systems, in this paper we explore the combined effects of activity and chirality on pattern formation within active chiral liquid crystals.…”