Biomedical Engineering Reference
In-Depth Information
22.5.2.3 Induced Protein Aggregation
Although. the. exact. trigger. of. protein. unfolding. at. the. particle. surface. is. unknown,. it.
might. involve. contact. forces,. such. as. the. release. of. free. surface. energy. through. surface.
reconstruction..An.example.might.be.relaxation.of.the.particle.crystal.structure.through.
protein. binding.
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. Similarly,. it. is. possible. that. electron. coninement. or. the. formation. of.
electron-hole. pairs. at. the. material. surface. could. lead. to. cleavage. of. structural. bonds. or.
covalent.cross-linking.of.protein.domains.
In.one.studied.experimental.model,.nanoparticles.act.as.catalysts.exposing.protein.inter-
action.domains.that.induce.aggregation.through.hydrogen.bonding.and.the.formation.of.
ibrils..For.example,.human.β2.microglobulin.ibrillation.occurs.on.the.surfaces.of.cerium.
oxide. and. copolymer. nanoparticles. and. Carbon. Nano. Tabes. (CNTs).
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. Such. aggregation.
would.have.serious.implications.for.maintaining.protein.functionality.on.the.surface.of.a.
BSSC.electrode..It.remains.to.be.determined,.however,.whether.these.experimental.condi-
tions. can. be. duplicated. in. vivo,. where. competitive. binding. in. complex. biological. luids.
may.screen.the.nucleation.surface..Extrapolating.this.in.the.context.of.BSSCs,.the.use.of.
large.molecule.coadorbants.is.one.strategy.toward.stabilizing.photoactive.proteins.at.the.
solid-state.electrode.surface..Such.approaches.are.further.explained.in.Section.22.6.
22.5.2.4 Particle Curvature
Particle.curvature.and.total.surface.area.can.also.play.a.signiicant.role.in.how.solid.sur-
faces.affect.protein.folding..It.is.commonly.assumed.that.the.greatest.available.surface.area.
would.induce.more.biopolymer.unfolding;.however,.recent.studies.have.shown.that.larger.
nanoparticles. with. lower. radii. of. curvature. exhibited. greater. interactions. with. protein,.
resulting.in.more.pronounced.denaturization.
In. studies. done. by. Lundqvst. et. al.,
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. the. conformational. states. of. the. enzyme. human.
carbonic.anhydrase.I.(HCAI).were.measured.by.circular.dichromisim,.nuclear.magnetic.
resonance.(NMR),.AFM,.and.gel.permeation.as.they.were.introduced.to.food-grade.silica.
nanoparticles. of. 6,. 9,. and. 15. nm. independently.. It. was. shown. that. the. curvature. of. the.
solid.surface.inluenced.the.degree.of.conformational.change.induced.in.the.secondary.
structure.of.HCAI..The.larger,.15.nm.diameter,.induced.conformational.changes.approxi-
mately. sixfold. higher. than. the. enzymes. introduced. to. the. 6. nm. suspensions.. In. con-
trast,. the. tertiary. structures. remained. very. similar. for. all. particles. and. not. as. affected.
by. the. silica. nanoparticle. curvatures.. This. effect. was. also. noted. by. the. Somasundaran.
group. when. studying. adsorption. characteristics. of. bovine. serum. albumin. on. hematite.
nanoparticles.
It.is.currently.hypothesized.that.the.relatively.smaller.radii.of.curvature.afforded.by.the.
larger.particles.allows.more.interactions.between.the.particle.surface.and.portions.of.the.
protein,.while.a.smaller.particle.has.a.smaller.particle/protein.contact.area..This.seems.to.
suggest.that,.in.BSSC.applications,.protein.degradation.may.be.retarded.simply.by.using.
smaller. nanostuctures. as. electrode. supports.. However,. these. studies. have. been. done. at.
protein.concentrations.between.0.5.µm.and.0.3.mM,.and.at.protein-to-nanoparticle.ratios.
ranging. from. 0.25:1. to. 1:1. in. suspension.. While. these. studies. yield. informative. results.
on.protein-nanoparticle. interactions,.they.are.still.a.distant.model. of.a.dye-.or.biosensi-
tized.electrode.surface..The.exact.mechanisms.of.interaction.between.nanoparticles.and.
proteins. remain. to. be. determined.. This. is. even. more. so. in. the. case. of. long-range. solid-
state.surfaces.with.unique.nanoscale.curvatures..These.conditions.yield.environments.on.
which.the.conformational.dynamics.of.photoactive.proteins.have.yet.to.be.explored.
