Towards a quantitative understanding of mitotic spindle assembly and mechanics

Abstract

SummaryThe 'simple' view of the mitotic spindle is that it self-assembles as a result of microtubules (MTs) randomly searching for chromosomes, after which the spindle length is maintained by a balance of outward tension exerted by molecular motors on the MTs connecting centrosomes and chromosomes, and compression generated by other motors on the MTs connecting the spindle poles. This picture is being challenged now by mounting evidence indicating that spindle assembly and maintenance rely on much more complex interconnected networks of microtubules, molecular motors, chromosomes and regulatory proteins. From an engineering point of view, three design principles of this molecular machine are especially important: the spindle assembles quickly, it assembles accurately, and it is mechanically robust -yet malleable. How is this design achieved with randomly interacting and impermanent molecular parts? Here, we review recent interdisciplinary studies that have started to shed light on this question. We discuss cooperative mechanisms of spindle self-assembly, error correction and maintenance of its mechanical properties, speculate on analogy between spindle and lamellipodial dynamics, and highlight the role of quantitative approaches in understanding the mitotic spindle design.

Complex Fluids and Soft Structures in the Human Body

“…Overall, with appropriate tuning of the spatial gradients, these models were able to recapitulate experimentally observed features of microtubule plus-end dynamics and kinetochore separation. However, none of the models explicitly consider the physical properties of the chromatin spring (for a review see the article by Mogilner and Craig [206]) which is one focus of the Bloom lab.…”

“…It is well known that as the kMTs grow and shorten, they "probe" space until they capture the chromosomes in a process rightly called search-and-capture [206,219,220]. The dynamic instability leading to growth/shrinkage of kMTs is included in the model; however the attachment/detachment dynamics are not included, i.e., the model assumes that the chromosomes are attached to the kMTs at all times.…”

Physical Determinants of Bipolar Mitotic Spindle Assembly and Stability in Fission Yeast

“…Important previous work has modeled aspects of spindle function and chromosome segregation (46,47) but not the establishment of bipolarity. Previous aspects of spindle function that have been modeled mathematically include spindle elongation and force balance (27,28,30,(48)(49)(50), the formation and maintenance of antiparallel MT overlaps (35,36,51,52), MT bundling and sliding (26,(53)(54)(55)(56)(57)(58), spindle pole focusing (29,49,59,60), spindle movements and positioning (44,(61)(62)(63)(64)(65)(66), spindle length and shape (25,26,31,(67)(68)(69)(70)(71), and spindle assembly (53,54,69,(72)(73)(74).…”

Mechanisms of plant spindle formation

“…Here, we argue that the same basic principles of spindle formation apply to plants but with the addition of the preprophase band that facilitates the orientation of spindles (Lloyd and Chan 2006;Bannigan et al 2008) and a heavier reliance on kinetochores as organizing centers (O'Connell and Khodjakov 2007;Mogilner and Craig 2010). We emphasize that this perspective is necessarily based on a very small plant literature and relies heavily on data from animals.…”