2018 journal article
The Spindle: Integrating Architecture and Mechanics across Scales
Trends in Cell Biology, 28(11), 896–910.
To perform its function, the spindle must be dynamic and flexible and yet able to generate force and maintain its integrity. Active and passive molecular force generators build and maintain the spindle. New approaches are revealing new properties of each, for example, how total force output scales with the number of force generators. Molecular motors can build diverse microtubule organization modules, for example, by selectively pulling on microtubule ends or by selectively acting on antiparallel microtubule arrangements. Physical perturbations reveal how spindle material properties vary with the axis and timescale of force application, and that the spindle locally bears the load of chromosome movement. Spindle self-organization connects scales from nanometers to tens of micrometers, and from tens of milliseconds to an hour. The robust function of the spindle emerges from the feedback between its architecture, dynamics, and mechanics across scales. The spindle segregates chromosomes at cell division, and its task is a mechanical one. While we have a nearly complete list of spindle components, how their molecular-scale mechanics give rise to cellular-scale spindle architecture, mechanics, and function is not yet clear. Recent in vitro and in vivo measurements bring new levels of molecular and physical control and shed light on this question. Highlighting recent findings and open questions, we introduce the molecular force generators of the spindle, and discuss how they organize microtubules into diverse architectural modules and give rise to the emergent mechanics of the mammalian spindle. Throughout, we emphasize the breadth of space and time scales at play, and the feedback between spindle architecture, dynamics, and mechanics that drives robust function. The spindle segregates chromosomes at cell division, and its task is a mechanical one. While we have a nearly complete list of spindle components, how their molecular-scale mechanics give rise to cellular-scale spindle architecture, mechanics, and function is not yet clear. Recent in vitro and in vivo measurements bring new levels of molecular and physical control and shed light on this question. Highlighting recent findings and open questions, we introduce the molecular force generators of the spindle, and discuss how they organize microtubules into diverse architectural modules and give rise to the emergent mechanics of the mammalian spindle. Throughout, we emphasize the breadth of space and time scales at play, and the feedback between spindle architecture, dynamics, and mechanics that drives robust function. force that consumes energy and that can drive self-organization by transducing chemical energy into mechanical work. system in which the individual units are internally driven and energy consuming. pair of microtubules oriented such that their plus and minus ends point in opposite directions. design and construction of a physical structure. assembly of microtubules where ends are gathered together to form a star shape. specialized protein layer attached to the inner surface of the cell membrane that helps give the cell its overall shape. change in parts over time, such as movement, turnover, growth, or shrinkage. ability of a structure, by storing energy, to return to its original shape after being deformed. characteristic of a phenomenon whereby interactions among smaller components give rise to larger entities that exhibit properties that the smaller components do not exhibit. molecular-scale resistance that opposes motion and dissipates energy. protein structure linking chromosomes to spindle microtubules. parallel bundle of microtubules and associated proteins binding kinetochores at their plus ends and anchoring chromosomes in the spindle. force to which a given object is subjected. supporting force transmission. properties that define the response of a material to force. generation of, response to, or transmission of mechanical force. force that does not consume energy but resists object deformation in space and time. property of an object to permanently retain its deformed shape after transient force on it is removed. dimensionless value that measures the ratio of inertial forces (tendency of an object to continue its same motion under no force) to viscous forces (tendency of a fluid to resist motion of an object moving through it). order arising from self-driven parts that consume energy. bipolar array of microtubules that mediates chromosome segregation at cell division. spindle extremity, where many microtubule minus ends focus together in mammalian cells. rigidity of a structure, that is, the extent to which it resists deformation in response to force. property of materials that exhibit both viscous (i.e., frictional) and elastic characteristics when deformed. measure of resistance that opposes motion and dissipates energy, associated with structural rearrangements that lead to shape changes that remain. shape-dependent value that reflects the viscous resistance of an object moving through a fluid.