Biomedical Engineering Reference
In-Depth Information
4.3.3 Microtubules
In. 1998,. the. determination. of. the. long-sought. high-resolution. crystal. structure. of. the.
α-/β-tubulin. heterodimer,. the. building. block. of. microtubules,. provided. the. framework.
for. insights. into. dynamics,. drug. binding,. and. self-assembly. of. microtubules. (Erickson,.
1975;.Nogales.et.al.,.1998;.Downing,.2000;.Nogales.and.Wang,.2006)..Microtubules.in.vivo.
are.typically.25.nm.in.diameter.and.composed.of.13.parallel.protoilaments.of.head.to.tail.
associated.α-/β-tubulin.heterodimers,.8.nm.in.length.and.4.nm.wide..The.heterodimeric.
subunits. generate. polarity. in. the. structure,. referred. to. as. minus-. or. plus-ends.. Decades.
of.elegant.studies.revealed.that.protoilament.plus-ends.that.associate.near.chromatin.or.
the.cell.periphery.terminate.in.β-tubulin,.while.microtubule.minus-ends.found.at.spindle.
poles. or. microtubule. organizing. centers. (MTOCs). terminate. in. α-tubulin.. Microtubules.
are. highly. dynamic. polymers. that. grow,. shrink,. pause,. or. transition. between. stages. by.
elongation.or.catastrophe.and.as.such.can.be.viewed.as.ancient.biological.motors.(McIntosh.
et. al.,. 2010).. Microtubule. assembly. and. disassembly. is. complex. and. involves. transient.
polymer.intermediates.that.include.sheets.and.ring.structures.versus.the.simple.addition.
or.removal.of.subunits.(Nogales.and.Wang,.2006)..Additional.complexity.in.microtubule.
dynamics.and.protein.association.are.present.since.multiple.classes.of.α-.and.β-tubulins.
exist. in. cells. and. posttranslational. modiications. may. be. present. that. vary. in. type. and.
extent.(Nogales,.2000)..Detyrosination,.acetylation,.and.certain.phosphorylation.events.on.
tubulins.are.thought.to.enhance.microtubule.stability..This.occurs,.in.part,.by.inluencing.
protein-protein. interactions. that. includes. microtubule-associated. proteins. (MAPs).. An.
alternative.means.to.regulate.microtubule.dynamics.is.through.the.use.of.chemical.agents.
(Downing,.2000),.including.the.microtubule.stabilizing.drug,.paclitaxel.(Taxol™).
4.4 Application of Molecular Motors in Nanotechnology
4.4.1 ingenuity through Dynamics in Nanodevices
Applications.for.nanodevices.generally.have.a.need.to.incorporate.multiple.capabilities.
and. apply. a. variety. of. natural. or. man-made. elements.. Capabilities. might. include. the.
ability.to.transport,.sort,.and.organize.as.well.as.control.elements.for.directional.guidance,.
cargo. loading,. unloading,. and. motion.. Natural. elements. include. chemicals,. proteins,.
and. nucleic. acids. and. are. often. combined. with. man-made. functionalized. substrates.
and. nanoparticles.. Assembly. line. designs. might. incorporate. either. a. multistep. process.
or. instead. reduce. the. problem. of. interconnects. by. acting. through. the. use. of. a. single.
highly.modiied.microtubule..The.latter.could.be.generated.through.stepwise.control.of.
microtubule. assembly. using. modiied. tubulin. building. blocks. that. containing. speciic.
interaction.sites.for.each.cargo.component..The.desired.result.would.be.a.predetermined.
and. highly. eficient. assembly. line.. It. is. clear. that. applications. will. be. limited. only. by.
the. creative. inspiration. applied. to. these. elements.. Proposed. technologies. include.
miniaturized. factories. or. actuators,. self-healing. along. with. novel. woven. materials,.
self-sorting. of. intricate. collections. of. molecules,. targeted. delivery,. biosensing,. and.
environmental.monitoring.(for.review,.see.Hess.and.Vogel,.2001;.Goel.and.Vogel,.2008)..
New. emerging. devices. include. “pharmacytes,”. a. term. coined. for. self-powered. drug.
delivery.devices.(Cohen.et.al.,.2005;.Freitas,.2006);.smart.dust.sensors.(Fischer.et.al.,.2009);.
