Comparative Studies of Microtubule Mechanics with Two Competing Models Suggest Functional Roles of Alternative Tubulin Lateral Interactions

dc.contributorVirginia Techen
dc.contributor.authorWu, Z. H.en
dc.contributor.authorNogales, Evaen
dc.contributor.authorXing, Jianhuaen
dc.contributor.departmentBiological Sciencesen
dc.description.abstractThe dynamic assembly and disassembly of microtubules and the mechanical properties of these polymers are essential for many key cellular processes. Mathematical and computational modeling, especially coupled mechanochemical modeling, has contributed significantly to our understanding of microtubule dynamics. However, critical discrepancies exist between experimental observations and modeling results that need to be resolved before further progress toward a complete model can be made. Open sheet structures ranging in length from several hundred nanometers to one micron have often been observed at the growing ends of microtubules in in vitro studies. Existing modeling studies predict these sheet structures to be short and rare intermediates of microtubule disassembly rather than important components of the assembly process. Atomic force microscopy (AFM) studies also reveal interesting step-like gaps of the force-indentation curve that cannot yet be explained by existing theoretical models. We have carried out computational studies to compare the mechanical properties of two alternative models: a more conventional model where tubulin dimers are added directly into a microtubule lattice, and one that considers an additional type of tubulin lateral interaction proposed to exist in intermediate sheet structures during the microtubule assembly process. The first model involves a single type of lateral interactions between tubulin subunits, whereas the latter considers a second type that can convert to the canonical lateral contact during microtubule closure into a cylinder. Our analysis shows that only the second model can reproduce the AFM results over a broad parameter range. We propose additional studies using different sizes of AFM tips that would allow to unambiguously distinguish the relative validity of the two models.en
dc.description.sponsorshipThomas F. Jeffress and Kate Miller Jeffress Memorial Trusten
dc.description.sponsorshipNational Science Foundation EF-1038636en
dc.description.sponsorshipNational Institute of General Medical Sciences GM051487en
dc.identifier.citationWu, Zhanghan; Nogales, Eva; Xing, Jianhua, "Comparative Studies of Microtubule Mechanics with Two Competing Models Suggest Functional Roles of Alternative Tubulin Lateral Interactions," Biophysical Journal 102(12), 2687-2696 (2012); doi: 10.1016/j.bpj.2012.05.003en
dc.publisherCELL PRESSen
dc.rightsIn Copyrighten
dc.subjectthermal fluctuationsen
dc.subjectdynamic instabilityen
dc.subjectpersistence lengthen
dc.titleComparative Studies of Microtubule Mechanics with Two Competing Models Suggest Functional Roles of Alternative Tubulin Lateral Interactionsen
dc.title.serialBiophysical Journalen
dc.typeArticle - Refereeden
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