4.16 Mechanical Forces in Mitosis

Abstract

Mitosis, the process by which the genome is segregated equally during cell division, is an intrinsically mechanical process. Although we now have a nearly complete list of molecules essential to cell division, how these molecules generate the emergent mechanical behavior remains a frontier. We begin by reviewing the basic architecture and dynamics of the mitotic spindle, the cellular assembly that segregates chromosomes in eukaryotes. We then review elementary force producing mechanisms in the spindle, and models for emergent mechanical behavior. We then discuss two processes that epitomize the complex mechanics of mitosis emerging from integration of simpler molecular functions. First, we focus on the problem of spindle length determination. How do nanometer-size building blocks assemble to form a spindle structure several microns in length to segregate genome copies far apart? Second, we focus on the mechanical architecture of the interface between chromosomes and spindle microtubules. The kinetochore is the macromolecular machine linking chromosomes to microtubules. How does it hold on to dynamic microtubules, and how does the kinetochore-microtubule interface generate force to move chromosomes? Throughout this chapter, we emphasize key missing data that notably includes quantitative values of forces, and how they vary as a function of position, within the spindle and kinetochore.