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Modulating enzyme activity with functionalized graphene oxide by ferujkll sdff
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Modulating enzyme activity with functionalized graphene oxide |
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Modulating enzyme activity with functionalized graphene oxide ( Nanowerk Spotlight ) One area of nanobiotechnology is concerned with designing andengineering suitable nanomaterials for biological applications.Although nanobiology researchers have frequently reported variouseffects of nanomaterials on biomolecules, cells, tissues, andanimals, the mechanisms behind these effects have rarely beenexplored – despite the fact that an understanding ofinteractions between nanomaterials and biomolecules is offundamental importance for this field. One type of biomolecules, enzymes, regulate almost all chemicalreactions involved in numerous biological processes in livingorganisms and are also widely used in research and industry –pharmaceutical and medical, food and environmental, biofuels andlife sciences. "Regulation of enzyme activity and stability is very importantand has always attracted great attention" Rui Peng , an associate professor in the Institute of Functional Nano & SoftMaterials at Soochow University in Suzhou, PR China, tellsNanowerk. "Various enzyme regulators, ranging from proteins,peptides, and synthetic organic molecules, have been discovered.Recently, nanomaterials evolve as promising alternatives for enzymemodulation.
Nanomaterials provide large surface areas forbiomolecule adsorption and can be engineered to present multiplesurface functional groups for interacting with biomolecules, suchas enzymes and/or their substrates." In a recent study, Peng together with her collaborator Zhuang Liu , a professor of chemistry, and their teams, started to explore theinteractions between functionalized graphene oxide and serineproteases, a large family of enzymes with important biomedical andindustrial applications. They reported their findings the May 10,2012 online edition of ACS Nano ( "Functionalized Graphene Oxide in Enzyme Engineering: ASelective Modulator for Enzyme Activity and Thermostability" ). The researchers point out that, to their best knowledge, this workis the first to successfully report the use of functionalizedgraphene oxide as an enzyme modulator with positive effects; highefficiency; and great selectivity for both the enzyme (trypsin) andthe substrate (phosphorylated proteins). "More importantly, we extended our investigation to explorethe mechanism behind the modulation, and identified two involvingfactors which led us to a hypothesis of possible functions ofPEGylated graphene oxide (GO-PEG) in the digestion reaction,"says Peng.
"Although further work is required, our workhighlights that the interactions of nanomaterials withbiomacromolecules, in general, can be regulated through and areclosely associated with their surface chemistry and/ornanointerfaces." Many nanomaterials, before surface modification – i.e.functionalization – possess rather hydrophobic surfaces,resulting in poor dispersibility in water and physiologicalsolutions, as well as poor biocompatibility. For example, as shownin the Chinese team's work, the unfunctionalized graphene oxidedramatically inhibits enzyme activity, likely due to thenonspecific binding of enzyme proteins on graphene oxide viahydrophobic interactions, resulting in possible blocking ordenaturing of the enzyme active center. Researchers use functionalization to improve biocompatibility ofthese nanomaterials and, while doing so, alter their surfacechemistry. "This could potentially alter the way they interact with othermaterials and/or biomolecules, leading to newly developed functions– our GO-PEGs with different PEGylations just provedthat" says Peng.
Graphene oxide nanosheets used in the study: schemes (a), AFMimages (b), and dispersibility in water and PBS. (Reprinted withpermission from American Chemical Society) In their work, the team investigated the effects of two types ofPEGylated GO nanosheets with free amines on three important serineproteases: trypsin, chymotrypsin, and proteinase K. Both nanosheetssignificantly improved trypsin activity and thermostability, whileshowing barely any effect on chymotrypsin or proteinase K. Peng points out that either blocking the functional amino groups orreplacing the two-dimensional graphene oxide with one-dimensionalsingle-walled carbon nanotubes abolished the stimulatory effect,suggesting the involvement of both the terminal amines on polymercoatings and the unique 2-D structure of graphene oxide.
"Detailed enzyme kinetics analysis revealed that PEGylated GOfunctions at both the initiation step and later steps along thereaction process," says Peng. "We also found that atleast up to 43-fold of reaction acceleration induced by PEGylatedGO could be achieved depending on the substrateconcentration." Going forward, the biggest challenge for the scientists is that sofar they cannot control the synthesis and surface modification ofthese nanomaterials as precisely as they do with proteins (throughgene/protein engineering); something which might cause a certainlevel of uncertainty and difficulty when interpreting the results. "Therefore, from the materials side, better control in surfacechemistry, size, and morphology of nanomaterials is critical,"say Peng and Liu. By Michael Berger.
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