Measurement of the Force-Velocity Relation for Growing Microtubules

Dogterom, Marileen; Yurke, Bernard

doi:10.1126/science.278.5339.856

Cited by 498 publications

(547 citation statements)

References 33 publications

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“…When microtubules are assembled, exerting pushing forces as they grow, cells can become mobile if the assembly is at the leading edge. Forces generated by protein polymerization have been measured, and speculation that the interaction of the growing microtubule end with a specific attachment might modify the force (Dogterom and Yurke, 1997). If the force emanates from a focal adhesion point, one can imagine that the force generation will be differentially felt throughout the cell body, perhaps activating specific signaling systems.…”

Section: Cellular Architecture and Tensegritymentioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

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400

303

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Bone tissue has the capacity to adapt to its functional environment such that its morphology is "optimized" for the mechanical demand. The adaptive nature of the skeleton poses an interesting set of biological questions (e.g., how does bone sense mechanical signals, what cells are the sensing system, what are the mechanical signals that drive the system, what receptors are responsible for transducing the mechanical signal, what are the molecular responses to the mechanical stimuli). Studies of the characteristics of the mechanical environment at the cellular level, the forces that bone cells recognize, and the integrated cellular responses are providing new information at an accelerating speed. This review first considers the mechanical factors that are generated by loading in the skeleton, including strain, stress and pressure. Mechanosensitive cells placed to recognize these forces in the skeleton, osteoblasts, osteoclasts, osteocytes and cells of the vasculature are reviewed. The identity of the mechanoreceptor(s) is approached, with consideration of ion channels, integrins, connexins, the lipid membrane including caveolar and noncaveolar lipid rafts and the possibility that altering cell shape at the membrane or cytoskeleton alters integral signaling protein associations. The distal intracellular signaling systems on-line after the mechanoreceptor is activated are reviewed, including those emanating from G-proteins (e.g., intracellular calcium shifts), MAPKs, and nitric oxide. The ability to harness mechanical signals to improve bone health through devices and exercise is broached. Increased appreciation of the importance of the mechanical environment in regulating and determining the structural efficacy of the skeleton makes this an exciting time for further exploration of this area.

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Section: Cellular Architecture and Tensegritymentioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

400

303

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“…This persistent tip tracking has enabled us to measure the effects of continuous tension on MT dynamic parameters in a reconstituted system for the first time. In our assay, beads coated with the Dam1 complex are attached to the tips of individual dynamic MTs grown from stabilized seeds anchored to a glass coverslip 14,22, 23 (Fig. 1a).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…Indirect regulation through MT-modifying enzymes has been implicated in corrective detachment of aberrant kinetochore-MT attachments 19-21 , but it is unknown whether an analogous indirect mechanism also controls the lengths of MTs that remain persistently attached. Evidence for a simpler direct mechanism comes from cell-free assays showing that compressive force caused by pushing MT tips against glass barriers slows filament growth 22,23 , and that brief pulses of tension < 1 pN transmitted through avidin-biotin linkages can delay detachment of terminal subunits 24 . However, these approaches do not allow measurement of MT dynamic parameters under continuous tension, so their relevance to length control of kinetochore MTs-which are usually under tension 5, 25 -is uncertain.…”

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confidence: 99%

Tension applied through the Dam1 complex promotes microtubule elongation providing a direct mechanism for length control in mitosis

et al. 2007

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In dividing cells, kinetochores couple chromosomes to the tips of growing and shortening microtubule (MT) fibers 1, 2 and tension at the kinetochore-MT interface promotes fiber elongation 3-6 . Tension-dependent MT fiber elongation is thought to be essential for coordinating chromosome alignment and separation 1, 3, 7-10 , but the mechanism underlying this effect is unknown. Using optical tweezers, we applied tension to a model of the kinetochore-microtubule interface composed of the yeast Dam1 complex 11-13 bound to individual dynamic microtubule tips 14 . Higher tension decreased the likelihood that growing tips would begin to shorten, slowed shortening, and increased the likelihood that shortening tips would resume growth. These effects are similar to the effects of tension on kinetochore-attached microtubule fibers in many cell types, suggesting that we have reconstituted a direct mechanism for microtubule length control in mitosis.For decades, a central problem for biologists has been to understand how MT lengths are controlled during mitosis 15, 16 . MTs are protein polymers that switch stochastically between phases of assembly and disassembly, during which tubulin subunits are added or lost from the filament tips 1 . This behavior, called 'dynamic instability', can be described by four parameters: the speeds of growth and shortening, and the rates of switching from growth to shortening and from shortening to growth, transitions known as 'catastrophes ' and 'rescues' 1, 17 In dividing cells, chromosomes are linked to the tips of MT fibers through specialized structures called kinetochores and their movements are coupled to fiber growth and shortening 1, 2 . Remarkably, kinetochores maintain persistent, load-bearing attachments to microtubule tips even as the filaments assemble and disassemble under their grip 1, 2, 18 . Classic micromanipulation experiments show that tension at the kinetochore-MT interface promotes MT fiber elongation 3-6 , and this effect is widely believed to be essential for controlling fiber lengths and thereby coordinating chromosome alignment and separation 1, 3, 7-10, 16 . Very little is known about the mechanism underlying this tension-dependent length control. However, the dynamic behavior of kinetochore-attached MT tips 18 implies that the mechanism underlying tension-dependent length control in vivo may act by altering one or more of the parameters of dynamic instability in response to load.A key unanswered question is whether tension promotes elongation via an indirect mechanism, where force transmitted through load-bearing kinetochore components regulates the activity of separate MT-modifying components, or by a direct mechanism, where the load-bearing Correspondence should be addressed to C.L.A.. * These authors contributed equally to this work. NIH Public Access Author ManuscriptNat Cell Biol. Author manuscript; available in PMC 2009 May 13. Published in final edited form as:Nat Cell Biol. 2007 July ; 9(7): 832-837. doi:10.1038/ncb1609. NIH-PA Author ManuscriptNIH-P...

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“…Our result is that f is actually the mean repulsive force exerted on the filament growing end. There has been clear experimental evidence that both the assembly and disassembly of microtubular filaments can generate force; however, only limited quantitative data are available on the actual magnitude of these forces [20]. In the case of Sm-A filaments discussed here, we estimate the force exerted on the ends to be the order of 10 −1 piconewton.…”

mentioning

confidence: 91%

“…The forces associated with the assembly and disassembly of filaments may be of vital biological significance. For example, it has long been speculated that the motion of chromosomes during mitosis of the cell cycle is caused by the assembly and disassembly of cytoskeletal microtubes [20].…”

mentioning

confidence: 99%

Theory on quench-induced pattern formation: Application to the isotropic to smectic-Aphase transitions

Zhou

Ouyang

1998

Phys. Rev. E

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During catastrophic processes of environmental variations of a thermodynamic system, such as rapid temperature decreasing, many novel and complex patterns often form. To understand such phenomena, a general mechanism is proposed based on the competition between heat transfer and conversion of heat to other energy forms. We apply it to the smectic-A filament growth process during quench-induced isotropic to smectic-A phase transition. Analytical forms for the buckling patterns are derived and we find good agreement with experimental observation [Phys. Rev. E55 (1997) 1655]. The present work strongly indicates that rapid cooling will lead to structural transitions in the smectic-A filament at the molecular level to optimize heat conversion. The force associated with this pattern formation process is estimated to be in the order of 10 −1 piconewton.

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Measurement of the Force-Velocity Relation for Growing Microtubules

Cited by 498 publications

References 33 publications

Molecular pathways mediating mechanical signaling in bone

Molecular pathways mediating mechanical signaling in bone

Tension applied through the Dam1 complex promotes microtubule elongation providing a direct mechanism for length control in mitosis

Theory on quench-induced pattern formation: Application to the isotropic to smectic-Aphase transitions

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