Conformational mechanism for the stability of microtubule-kinetochore attachments.

Zsolt Bertalan, Caterina A M La Porta, Helder Maiato, Stefano Zapperi

Journal: Biophysical journal 2015;107(2):289-300

PMID: 25028871

Abstract

Regulating the stability of microtubule (MT)-kinetochore attachments is fundamental to avoiding mitotic errors and ensuring proper chromosome segregation during cell division. Although biochemical factors involved in this process have been identified, their mechanics still need to be better understood. Here we introduce and simulate a mechanical model of MT-kinetochore interactions in which the stability of the attachment is ruled by the geometrical conformations of curling MT-protofilaments entangled in kinetochore fibrils. The model allows us to reproduce, with good accuracy, in vitro experimental measurements of the detachment times of yeast kinetochores from MTs under external pulling forces. Numerical simulations suggest that geometrical features of MT-protofilaments may play an important role in the switch between stable and unstable attachments.

Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Address: Institute for Scientific Interchange Foundation, Torino, Italy.; Department of Biosciences, University of Milano, Milano, Italy.; Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal; Cell Division Unit, Department of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal.; Institute for Scientific Interchange Foundation, Torino, Italy; National Research Council of Italy, Istituto per l'Energetica e le Interfasi, Milano, Italy. Electronic address: [email protected].
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