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Inhibition of Microtubule Depolymerization by Osmolytes

Biomacromolecules

Bachand, George B.; Vandelinder, Virginia A.; Ko, Randy F.; Bouxsein, Nathan F.; Jain, Rishi

Microtubule dynamics play a critical role in the normal physiology of eukaryotic cells as well as a number of cancers and neurodegenerative disorders. The polymerization/depolymerization of microtubules is regulated by a variety of stabilizing and destabilizing factors, including microtubule-associated proteins and therapeutic agents (e.g., paclitaxel, nocodazole). Here we describe the ability of the osmolytes polyethylene glycol (PEG) and trimethylamine-N-oxide (TMAO) to inhibit the depolymerization of individual microtubule filaments for extended periods of time (up to 30 days). We further show that PEG stabilizes microtubules against both temperature- and calcium-induced depolymerization. Our results collectively suggest that the observed inhibition may be related to combination of the kosmotropic behavior and excluded volume/osmotic pressure effects associated with PEG and TMAO. Taken together with prior studies, our data suggest that the physiochemical properties of the local environment can regulate microtubule depolymerization and may potentially play an important role in in vivo microtubule dynamics.

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Dynamic assembly of polymer nanotube networks via kinesin powered microtubule filaments

Nanoscale

Paxton, Walter F.; Bachand, George B.; Gomez, Andrew G.; Henderson, Ian M.; Bouxsein, Nathan F.

In this study, we describe for the first time how biological nanomotors may be used to actively self-assemble mesoscale networks composed of diblock copolymer nanotubes. The collective force generated by multiple kinesin nanomotors acting on a microtubule filament is large enough to overcome the energy barrier required to extract nanotubes from polymer vesicles comprised of poly(ethylene oxide-b-butadiene) in spite of the higher force requirements relative to extracting nanotubes from lipid vesicles. Nevertheless, large-scale polymer networks were dynamically assembled by the motors. These networks displayed enhanced robustness, persisting more than 24 h post-assembly (compared to 4–5 h for corresponding lipid networks). The transport of materials in and on the polymer membranes differs substantially from the transport on analogous lipid networks. Specifically, our data suggest that polymer mobility in nanotubular structures is considerably different from planar or 3D structures, and is stunted by 1D confinement of the polymer subunits. Moreover, quantum dots adsorbed onto polymer nanotubes are completely immobile, which is related to this 1D confinement effect and is in stark contrast to the highly fluid transport observed on lipid tubules.

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Biomolecular motors in nanoscale materials, devices, and systems

Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology

Bachand, George B.; Bouxsein, Nathan F.; Vandelinder, Virginia A.; Bachand, Marlene B.

Biomolecular motors are a unique class of intracellular proteins that are fundamental to a considerable number of physiological functions such as DNA replication, organelle trafficking, and cell division. The efficient transformation of chemical energy into useful work by these proteins provides strong motivation for their utilization as nanoscale actuators in ex vivo, meso- and macro-scale hybrid systems. Biomolecular motors involved in cytoskeletal transport are quite attractive models within this context due to their ability to direct the transport of nano-/micro-scale objects at rates significantly greater than diffusion, and in the absence of bulk fluid flow. As in living organisms, biomolecular motors involved in cytoskeletal transport (i.e., kinesin, dynein, and myosin) function outside of their native environment to dissipatively self-assemble biological, biomimetic, and hybrid nanostructures that exhibit nonequilibrium behaviors such as self-healing. These systems also provide nanofluidic transport function in hybrid nanodevices where target analytes are actively captured, sorted, and transported for autonomous sensing and analytical applications. Moving forward, the implementation of biomolecular motors will continue to enable a wide range of unique functionalities that are presently limited to living systems, and support the development of nanoscale systems for addressing critical engineering challenges. © 2013 Wiley Periodicals, Inc.

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20 Results
20 Results