A UCLA-ledteam of chemists has developed a unique new coating for inorganic particles atthe nanoscale that may be able to disguise the particles as proteins — aprocess that allows particles to function as probes that can penetrate the celland light up individual proteins inside, and create the potential forapplication in a wide range of drug development, diagnostic tools andmedications.
The findingswill be published in the May 19 edition of the Journal of the American ChemicalSociety.
The organic coatings— short chains of stringed amino acids (peptides) — can be used to disguiseparticles called "quantum dots," "quantum rods" and "quantum "wires" soeffectively that the cells mistake them for proteins, even when the coatingsare used on particles that are inorganic and possibly even toxic.
"Thesepeptide coatings serve as 'Halloween costumes' for the particles, and trick thelive cell into thinking that the nanoparticles are benign, protein-likeentities," said Shimon Weiss, UCLA professor of chemistry and a member of theuniversity's California NanoSystems Institute. "As a result, we can use thesecoated particles to track the proteins in a live cell and conduct a range ofstudies at the molecular level, which is a major step toward using nanotechnologyto create practical applications for biology and medicine."
Particlesmade of semiconductors at the nanoscale (one-billionth of a meter, or about one‑thousandththe thickness of a human hair) have long found applications in the electronicand information technology industries. For example, the active part of a singletransistor on a Pentium silicon chip is a few tenths of a nanometer in size.The semiconductor laser used to read digital information on a CD or DVD has anactive layer of similar dimensions.
"Creating theability to import such electronic functions into the cell and meshing them withbiological functions could open tremendous new possibilities, both for basicbiological sciences and for medical and therapeutic applications," Weiss said.
One of theseelectronic functions is the emission of light called fluorescence. Using thenew coatings, Weiss' team has been able to solubilize and introduce into thecell different color quantum dots that can all be excited by a single bluelight source.
The colorencoding method is similar to the encoding of information that is sent down anoptical fiber, called "wavelength division multiplexing," or WDM. The peptidecoating technology could, in principle, color encode biology itself, by"painting" different proteins in the cell with different-color quantum dots.
The researchteam includes Weiss — the principal investigator — and graduate student FabienPinaud, along with UC Berkeley assistant research biochemist David S. King andHsiao‑Ping Moore, professor of molecular and cell biology.
Weiss andPinaud are developing methods to attach quantum dots of specific colors to thedifferent proteins on cells' surface and inside cells.
"Humans haveclose to 40,000 genes," Weiss said. "A large group of these genes operates atevery moment, in every single cell of our body, in very complicated ways. By painting a subset of proteins in the cellwith different color quantum dots, we can follow the molecular circuitry, thedynamic rearrangement of circuit nodes and the molecular interactions — or, inshort, observe the 'molecular dance' that defines life itself."
In additionto the capacity to paint and observe many different proteins with separatecolors, quantum dots can be used for the ultimate detection sensitivity:observing a single molecule. Until now, tracking and following a single proteinin the cell has been extremely challenging and was the equivalent of searchingfor the proverbial needle in a haystack.
By using thenew methods developed at UCLA, and observing with a fluorescence microscope andhigh-sensitivity imaging cameras, researchers can track a single protein taggedwith a fluorescent quantum dot inside a living cell in three dimensions andwithin a few nanometers of accuracy.
"This processis, in some ways, the molecular equivalent of using the global positioningsystem to track a single person anywhere on earth," Pinaud said. "We can useoptical methods to track several different proteins tagged with different-colorquantum dots, measure the distances between them and use those findings tobetter understand the molecular interactions inside the cell."
Particlesdisguised with the peptide coatings developed by the Weiss team can enter acell without affecting its basic functioning — creating a water-soluble andbiocompatible thin layer for the particles that can be targeted to bind toindividual proteins in the live cell.
"Since thepeptide-coated quantum dots are small, they have easy and rapid entry throughthe cell membrane," Pinaud said. "In addition, since multiple peptides ofvarious lengths and functions could be deposited on the same single quantumdot, we can easily envision the creation of 'smart' probes with multiplefunctions."
The Weissteamwork on coatings was inspired by nature.Some plants and bacteria cells evolved unique capabilities to blocktoxic heavy-metal ions as a strategy to clean up the toxic environment in whichthey grow. These organisms synthesize peptides, called phytochelatins, thatreduce the amount of toxic-free ions by strongly binding to inorganicnanoparticles made of the sequestered toxic salts and other products.
"Our peptidecoating bridges the inorganic chemistry world with the organic world on thenanometer scale," Weiss said. "Ideally, these coatings will be used to provideelectrical contact between nanoscale inorganic electronic devices andfunctional proteins, which would lead to the evolution of novel and powerful'smart drugs,' 'smart enzymes,' 'smart catalysts,' 'protein switches' and many otherfunctional hybrids of inorganic-organic substances.
"The possibilities are endless," Weiss said. "For example, justimagine the potential for this process in cancer treatment, if a hybridnanoparticle could be created that was specifically targeted to identify anddestroy cancer cells in the body."