ArticleMolecular systems biology2008
Reverse engineering of force integration during mitosis in the Drosophila embryo.
Article in Molecular systems biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Unveiling inter-embryo variability in spindle length over time: Towards quantitative phenotype analysis.PLoS computational biology · 2024Article
- Modeling spatiotemporally varying protein-protein interactions in CyLaKS, the Cytoskeleton Lattice-based Kinetic Simulator.The European physical journal. E, Soft matter · 2021Article
- Comparison of explicit and mean-field models of cytoskeletal filaments with crosslinking motors.The European physical journal. E, Soft matter · 2021Article
- Mechanical Mechanisms of Chromosome Segregation.Cells · 2021Review
- Article
- Reverse-engineering forces responsible for dynamic clustering and spreading of multiple nuclei in developing muscle cells.Molecular biology of the cell · 2020Article
- Mechanics of Multicentrosomal Clustering in Bipolar Mitotic Spindles.Biophysical journal · 2020Article
- Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling.eLife · 2020Article
- Bidirectional sliding of two parallel microtubules generated by multiple identical motors.Journal of mathematical biology · 2019Article
- Theory of Cytoskeletal Reorganization during Cross-Linker-Mediated Mitotic Spindle Assembly.Biophysical journal · 2019Article
- Mechanical positioning of multiple nuclei in muscle cells.PLoS computational biology · 2018Article
- Microtubule Sliding within the Bridging Fiber Pushes Kinetochore Fibers Apart to Segregate Chromosomes.Developmental cell · 2017Article
- Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast.Science advances · 2017Article
- Inferring the Forces Controlling Metaphase Kinetochore Oscillations by Reverse Engineering System Dynamics.PLoS computational biology · 2015Article
- Building the Microtubule Cytoskeleton Piece by Piece.The Journal of biological chemistry · 2015Review
- Emergent Properties of the Metaphase Spindle.Cold Spring Harbor perspectives in biology · 2015Review
- Cell size modulates oscillation, positioning and length of mitotic spindles.Scientific reports · 2015Article
- Article
- Micromechanics of the vertebrate meiotic spindle examined by stretching along the pole-to-pole axis.Biophysical journal · 2014Article
- Highly Transient Molecular Interactions Underlie the Stability of Kinetochore-Microtubule Attachment During Cell Division.Cellular and molecular bioengineering · 2013Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
The mitotic spindle is a complex macromolecular machine that coordinates accurate chromosome segregation. The spindle accomplishes its function using forces generated by microtubules (MTs) and multiple molecular motors, but how these forces are integrated remains unclear, since the temporal activation profiles and the mechanical characteristics of the relevant motors are largely unknown. Here, we developed a computational search algorithm that uses experimental measurements to 'reverse engineer' molecular mechanical machines. Our algorithm uses measurements of length time series for wild-type and experimentally perturbed spindles to identify mechanistic models for coordination of the mitotic force generators in Drosophila embryo spindles. The search eliminated thousands of possible models and identified six distinct strategies for MT-motor integration that agree with available data. Many features of these six predicted strategies are conserved, including a persistent kinesin-5-driven sliding filament mechanism combined with the anaphase B-specific inhibition of a kinesin-13 MT depolymerase on spindle poles. Such conserved features allow predictions of force-velocity characteristics and activation-deactivation profiles of key mitotic motors. Identified differences among the six predicted strategies regarding the mechanisms of prometaphase and anaphase spindle elongation suggest future experiments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.