Chromosome Segregation Controlled by External Mechanical Impulse in a Mammalian Cell

Abstract

During cellular development and growth, cells experience various impacts from physical environments, such as the exertion of the external force. It is not known, however, whether and how the external force affects the mechano-chemical processes in cell division. 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 external force that either facilitate or delay anaphase onset, depending on the direction of force and the extent of cell compression. 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 hinders chromosome segregation and is coupled with the activation of the spindle assembly checkpoint, which impedes the degradation of mitotic proteins, e.g., cyclin B. We propose that the external mechanical impulse, which modulates tension on sister chromatids, can control metaphase progression through different mechano-chemical cellular reactions.A part of this work was performed in collaboration with Yasuhiko Terada in Waseda University, and with Kenta Kuwana, Tetsuo Kan and Isao Shimoyama in the University of Tokyo. This work was supported in part by Grant-in-Aid for Scientific Research on Priority Areas (to T.I.), Grants-in-Aid for Specially Promoted Research and Scientific Research (S) (to S.I.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.