Biology subjects

Pavin, N.

Publications and source records attributed to Pavin, N..

4 recordsLinked to original sources

bioRxiv2018

Pivoting of microtubules driven by minus end directed motors leads to their alignment to form an interpolar bundle

At the beginning of mitosis, the cell forms a spindle made of microtubules and associated proteins to segregate chromosomes. An important part of spindle architecture is a set of antiparallel microtubule bundles connecting the two spindle poles. A key question is how microtubules extending at arbitrary angles form an antiparallel interpolar bundle. Here we show that microtubules meet at an oblique angle and subsequently rotate into antiparallel alignment. By combining experiments with theory, we show that microtubules from each pole search for those from the opposite pole by performing random angular movement. Upon contact of two microtubules, they slide sideways along each other towards the minus end, which we interpret as the action of minus end directed Cut7/kinesin-5 motors. In conclusion, random rotational motion helps microtubules from the opposite poles to find each other and subsequent accumulation of motors allows them to generate forces that drive interpolar bundle formation.

cell biology↗

bioRxiv2017

Chromosome loss rate in cells of different ploidy can be explained by spindle self-organization

The mitotic spindle segregates chromosomes and minimizes chromosome loss for the specific number of chromosomes present in an organism. In Saccharomyces cerevisiae, for example, haploid and diploid cells are part of the sexual life cycle and have a thousand times lower rate of chromosome loss than tetraploid cells. Currently it is unclear what constrains the number of chromosomes that can be segregated with high fidelity in an organism. Here we developed a mathematical model to study if different rates of chromosome loss in cells with different ploidy can arise from changes in (1) spindle dynamics and (2) a maximum duration of mitotic arrest, after which cells enter anaphase. Our model reveals how small increases in spindle assembly time can result in exponential differences in rate of chromosomes loss between cells of increasing ploidy and predicts the maximum duration of mitotic arrest.

evolutionary biology↗

bioRxiv2017

The mitotic spindle is chiral due to torques generated by motor proteins

Mitosis relies on forces generated in the spindle, a micro-machine composed of microtubules and associated proteins1,2. Forces are required for the congression of chromosomes to the metaphase plate and separation of chromatids in anaphase3-6. However, torques may also 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 follow a left-handed helical path, which cannot be explained by forces but rather by torques acting in the bundles. STED super-resolution microscopy, as well as confocal microscopy, of human spindles shows that the bundles have complex curved shapes. The average helicity of the bundles with respect to the spindle axis is 1.2{degrees}/m. Inactivation of kinesin-5 (Eg5/Kif11) abolished the chirality of the spindle, suggesting that this motor generates the helical shape of microtubule bundles. To explain the observed shapes, we introduce a theoretical model for the balance of forces and torques acting in the spindle, and show that torque is required to generate the helical shapes. We conclude that torques generated by motor proteins, in addition to forces, exist in the spindle and determine its architecture.

cell biology↗

bioRxiv2017

Pivot-and-bond model explains microtubule bundle formation

During mitosis, bundles of microtubules form a spindle, but the physical mechanism of bundle formation is still not known. Here we show that random angular movement of microtubules around the spindle pole and forces exerted by passive cross-linking proteins are sufficient for the formation of stable microtubule bundles. We test these predictions by experiments in wild-type and ase1{Delta} fission yeast cells. In conclusion, the angular motion drives the alignment of microtubules, which in turn allows the cross-linking proteins to connect the microtubules into a stable bundle.

biophysics↗