Angewandte Chemie International Edition
Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2004, 43 (23), 3048—3050
Fishing for Proteins
Magnetic gold and nickel nanorods for the separation of biomolecules
Little rods made of nickel and gold sound like something from a jeweler’s shop, but with an average diameter of only about 330 nanometers, the rods in this case are far too small to make fashionable jewelry. Why then have Chad A. Mirkin and his team at Northwestern University in Evanston (USA) gone to the trouble of making nickel rods with gold tips? For the biosciences—the magnetic nanorods are designed to help in the separation of biomolecules.
Precious metals are known to specifically bind to biomolecules with particular groups of atoms. Nickel, for example, binds to the amino acid histidine. Marking with histidine is a common technique for obtaining larger quantities of a protein for, amongst other things, structure determination. The gene that codes for the desired protein is inserted into a microorganism, which then produces the protein. Prior to insertion, the gene is modified so that a tail made of several histidine building blocks is added to the protein. Nickel-containing separation columns are then used to separate the histidine-marked proteins from the complex mixture of cell components.
The Northwestern University researchers thought this method could be made more elegant if they used nickel structures in miniature. They decided on nanorods, which can be produced with relative ease by the electrochemical deposition of nickel into the pores of an aluminum oxide membrane. Another electrodeposition step then furnishes the nickel rods with two golden ends. These gold caps merely serve to protect the nickel rods after the electrodeposition, when the silver layer used as an electrode is etched away from the membrane.
Proteins marked with histidine bind just as tightly to the nickel portion of the rods as they do to the nickel separation columns, but the rods have a number of advantages: They act as a scaffold, which provides a very large surface for the biospecific recognition processes. At the same time, the rods behave as part of the solution, in that they are evenly distributed, which makes them more accessible to the proteins than the material in a column. Because the rods are magnetic, they can easily and effectively be removed from the solution by a magnet on the wall of the vessel. A special buffer solution is subsequently used to disrupt the interactions between nickel and histidine, setting the proteins free.
The gold caps can also be used for binding to biomolecules, thus making the nanorods even more useful: gold specifically binds to molecules rich in thiol groups (–SH).