title: Mechanical impulses can control metaphase progression in a mammalian cell.
abstract: Chromosome segregation machinery is controlled by mechanochemical regulation. Tension in a mitotic spindle, which is balanced by molecular motors and polymerization-depolymerization dynamics of microtubules, is thought to be essential for determining the timing of chromosome segregation after the establishment of the kinetochore-microtubule attachments. It is not known, however, whether and how applied mechanical forces modulate the tension balance and chemically affect the molecular processes involved in chromosome segregation. Here we found that a mechanical impulse externally applied to mitotic HeLa cells alters the balance of forces within the mitotic spindle. We identified two distinct mitotic responses to the applied mechanical force that either facilitate or delay anaphase onset, depending on the direction of force and the extent of cell compression. An external mechanical impulse that physically increases tension within the mitotic spindle accelerates anaphase onset, and this is attributed to the facilitation of physical cleavage of sister chromatid cohesion. On the other hand, a decrease in tension activates the spindle assembly checkpoint, which impedes the degradation of mitotic proteins and delays the timing of chromosome segregation. Thus, the external mechanical force acts as a crucial regulator for metaphase progression, modulating the internal force balance and thereby triggering specific mechanochemical cellular reactions.
authors.affiliation: Department of Physics, Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Itabashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Terada
authors.forename: Kenta
authors.initials: K
authors.lastname: Kuwana
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kan
authors.forename: Isao
authors.initials: I
authors.lastname: Shimoyama
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Ishiwata
mesh_terms: D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D064246:Mad2 Proteins; D008677:Metaphase; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001324:Autoantigens; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins; D049452:Green Fluorescent Proteins; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases