title: Pericentric chromatin loops function as a nonlinear spring in mitotic force balance.
abstract: The mechanisms by which sister chromatids maintain biorientation on the metaphase spindle are critical to the fidelity of chromosome segregation. Active force interplay exists between predominantly extensional microtubule-based spindle forces and restoring forces from chromatin. These forces regulate tension at the kinetochore that silences the spindle assembly checkpoint to ensure faithful chromosome segregation. Depletion of pericentric cohesin or condensin has been shown to increase the mean and variance of spindle length, which have been attributed to a softening of the linear chromatin spring. Models of the spindle apparatus with linear chromatin springs that match spindle dynamics fail to predict the behavior of pericentromeric chromatin in wild-type and mutant spindles. We demonstrate that a nonlinear spring with a threshold extension to switch between spring states predicts asymmetric chromatin stretching observed in vivo. The addition of cross-links between adjacent springs recapitulates coordination between pericentromeres of neighboring chromosomes.
authors.affiliation: Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Stephens
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Haggerty
authors.forename: Paula A
authors.initials: PA
authors.lastname: Vasquez
authors.forename: Leandra
authors.initials: L
authors.lastname: Vicci
authors.forename: Chloe E
authors.initials: CE
authors.lastname: Snider
authors.forename: Fu
authors.initials: F
authors.lastname: Shi
authors.forename: Cory
authors.initials: C
authors.lastname: Quammen
authors.forename: Christopher
authors.initials: C
authors.lastname: Mullins
authors.forename: Julian
authors.initials: J
authors.lastname: Haase
authors.forename: Russell M
authors.initials: RM
authors.lastname: Taylor
authors.forename: Jolien S
authors.initials: JS
authors.lastname: Verdaasdonk
authors.forename: Michael R
authors.initials: MR
authors.lastname: Falvo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jin
authors.forename: M Gregory
authors.initials: MG
authors.lastname: Forest
authors.forename: Kerry
authors.initials: K
authors.lastname: Bloom
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D015825:Chromosomes, Fungal / Q000378:metabolism*; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D002843:Chromatin