Biomedical Engineering Reference
In-Depth Information
changes.to.amino.acids.through.the.alteration.of.embedded.instructions.in.their.genetic.
code.or.adding.functional.domains.through.addition.of.protein,.nucleic.acid,.or.synthetic.
associations..In.this.chapter,.we.begin.with.an.overview.of.the.complexity.of.biomolecular.
motors.and.the.cellular.cytoskeleton.components,.actin.microilaments.and.microtubules..
This.background.provides.a.foundation.for.an.in-depth.discussion.of.exciting.applications.
of.these.biological.components.in.innovative.biosynthetic.nanodevice.applications.
4.2.1 Molecular Motors of the Cellular Cytoskeleton
Decades.of.discovery.based.on.biological,.biophysical,.and.structural.analysis.of.motor.pro-
teins.would.not.have.been.possible.without.research.in.a.wide.range.of.model.organisms..
Mechanistic. studies. in. eukaryotes. are. enhanced. by. genetic. manipulation,. biochemical.
analysis,. and. time-lapse. live-cell. imaging. and. include. numerous. studies. in. yeasts. (pre-
dominantly. budding. yeast.
Saccharomyces cerevisiae
. and. ission. yeast.
Schizosaccharomyces
pombe
),. other. fungi. (including.
Neurospora crassa
. and.
Aspergillus nidulans
),. the. transpar-
ent. nematode.
Caenorhabditis elegans
,. the. fruit. ly.
Drosophila melanogaster
,. the. African. tree.
frog.
Xenopus laevis
,.and.mammals.(Sellers,.2000;.Lawrence.et.al.,.2004;.Miki.et.al.,.2005)..
Comparative. analysis. has. been. invaluable. to. help. determine. general,. conserved. mech-
anisms. versus. more. unique. or. species-speciic. requirements. in. motor. protein. complex-
ity.. Highly. conserved. mechanisms. reveal. natural. design-optimized. outcomes,. whereas.
multiple. mechanisms. generally. relect. a. high. degree. of. lexibility. and/or. specialization.
needed. in. the. process.. Molecular. motors. of. the. cytoskeleton. include. the. actin-binding.
myosin.motors.and.microtubule-binding.kinesin,.kinesin-like.proteins.(Klps),.and.dynein.
(Figure. 4.1).. Many. similar. concepts. are. used. in. discussing. these. motors. including. con-
served.structural.domains,.monomeric.or.multimeric.or.multiprotein.forms,.ATP.hydro-
lysis.and.force.generation,.processivity,.active.or.inactive.conformations,.and.regulation..
Motility.of.all.motors.is.not.yet.determined,.but.when.kinetic.data.are.present,.parameters.
of. directionality. may. also. include. back-stepping. or. non-uniform. step. sizes.. These. natu-
ral.motors.provide.inspiration.for.a.range.of.walking.molecules.to.be.used.in.combining.
nanotechnology. with. biosynthetic. designs. (von. Delius. and. Leigh,. 2011).. In. addition. to.
these.“tracking”.motors,.it.is.useful.to.follow.related.ields.of.study.on.chemical.motors.
and.non-tracking.multiprotein.motor.complexes.such.as.ATP.synthase,.the.ribosome,.and.
lagella.discussed.briely.herein.
4.2.2 Myosins: Actin-Dependent Motors
Myosin.was.the.irst.of.the.cytoskeleton.motor.proteins.to.be.identiied.(Pollard.and.Korn,.
1973).. It. was. followed. a. decade. later. by. discoveries. of. the. microtubule. motors,. conven-
tional. kinesin,. and. dynein. (Brady,. 1985;. Vale. et. al.,. 1985;. Schnapp. and. Reese,. 1989).. A.
complex.superfamily.of.myosins.containing.more.than.15.extended.groups.has.now.been.
revealed.(Morgan,.1995;.Cope.et.al.,.1996;.Sellers,.2000;.De.La.Cruz.and.Ostap,.2004)..Well-
studied. members. include. monomeric. myosin. I. involved. in. vesicle. transport,. myosin. II.
(conventional.myosin).responsible.for.muscle.contraction,.and.the.unconventional.dimeric.
myosin. V. and. dimeric. or. monomeric. myosin. VI. kinesin-like. motors. involved. in. vesicle.
and.organelle.transport.and.tethering.near.the.cell.periphery..The.scope.of.functions.for.
the.myosin.superfamily.are.extensive.and.include.additional.roles.in.cell.invasion,.signal.
transduction,. cytokinesis,. phagocytosis,. phototransduction,. and. stereocilia. movement.
(Salles. et. al.,. 2009;. Betapudi,. 2010;. Venkatachalam. et. al.,. 2010;. for. reviews,. see. Cheney.
and.Mooseker,.1992;.Sellers,.2000;.Krendel.and.Mooseker,.2005)..While.some.myosins.are.
