Biomedical Engineering Reference
In-Depth Information
many. diseases. are. associated. with. defects. in. signaling. via. membrane-bound. receptors,.
and.the.majority.of.therapeutic.drugs.presently.on.the.market.target.these.proteins.
Given.that.membrane.receptors.are.able.to.sense.molecules.with.great.precision,.there.
is. large. interest. in. utilizing. these. for. biosensor. applications.. As. an. example. of. recent.
advances.in.the.receptor-based.biosensor.ield,.the.present.review.will.focus.on.olfactory.
receptor.(OR).based.sensor.applications,.with.speciic.focus.on.cell-free.systems.and.incor-
poration.of.nanoscale.physical.detection.and.transduction.systems.
10.2 Biosensors
Biosensors.combine.the.use.of.a.biological.sensor.with.a.physical.transduction.mechanism,.
which. transmits. the. information. into. a. measurable. signal.. The. advantage. of. utilizing.
biological. molecules. as. sensors. is. that. evolution. has. provided. us. with. a. vast. variety. of.
different. biological. molecules. capable. of. recognizing. speciic. ligands. with. high. afinity..
Biosensors.have.been.constructed.using.biological.components.such.as.enzymes,.antibodies,.
nucleotides,.pores,.ion.channels,.and.receptors..This.review.will.focus.on.afinity-based.
biosensors,.which.take.advantage.of.the.binding.of.a.speciic.ligand/analyte.to.a.biological.
molecule..The.bulk.of.biosensors.in.this.category.currently.under.development.or.on.the.
market.are.based.on.antibody/antigen.binding.interactions,.taking.advantage.of.the.relative.
stability.of.antibodies.outside.of.the.cellular.environment..Similarly,.the.use.of.nucleotides.
and.aptamers.for.recognition.of.RNA.and.DNA.is.extensive.due.to.their.stability.and.ease.
of.conjugation.to.a.number.of.physical.substrates..(We.refer.the.reader.to.Chapters.2.and.
5.for.more.detail.)
The.unique.feature.of.a.receptor.is.that.it.has.evolved.to.interact.with.high.speciicity.
and.afinity.with.its.particular.ligand,.also.referred.to.as.analyte.in.the.biosensor.literature..
These.attributes.make.membrane-bound.receptors.attractive.targets.for.use.in.biosensor.
development.. Our. knowledge. of. membrane-protein. coupled. biosensors. has. increased.
dramatically.as.a.consequence.of.advances.made.in.the.ield.of.pore-forming.membrane.
proteins.in.these.applications.(e.g.,.gramicidin.and.α-hemolysin)..Much.of.the.knowledge.
on.plasma.membrane.immobilization.and.protein.stability.in.lipid.bilayers.stems.from.this.
literature.and.has.been.applied.to.the.receptor-biosensor.ield..Ion.channel.proteins.make.
attractive.biosensors.due.to.their.inherent.ability.to.transduce.an.electrochemical.signal.
that.can.be.manipulated.upon.ligand.binding..This.has.been.applied.to.the.sensing.of.a.
wide.variety.of.molecules,.ranging.from.toxins.to.nucleotides..Several.excellent.reviews.
exist.that.cover.the.current.state.of.membrane.pore.based.sensors.(Movileanu.2009,.Gu.and.
Shim.2010,.Liu.et.al..2010a,.Majd.et.al..2010,.Noy.2011,.Steller.et.al..2012)..In.addition,.Chapter.
6.delves.into.detail.regarding.the.use.of.nanopores.in.nucleotide.sequencing.applications.
10.3 Olfactory G-Protein Coupled Receptors
10.3.1 gPCr Signaling
Olfactory. receptors. belong. to. the. G-protein. coupled. receptors. (GPCRs).. GPCRs. are.
involved. in. numerous. signal. recognition. and. transduction. events. that. include. sensing.
