Credit: © 2007 ACS

Arrays of different proteins can be routinely immobilized on surfaces with micrometre precision and these so-called 'biochips' are used to investigate biomolecular interactions, with applications in medical diagnostics. Increasing the protein density of such arrays by patterning them at nanometre length scales may lead to miniaturized devices with improved sensitivity.

Researchers in the USA have now used rigid DNA scaffolds to organize proteins over distances as short as 32 nm. Hao Yan and co-workers1 from Arizona State University in Tempe made DNA tiles that self-assemble into rigid two-dimensional platforms that have protein-binding loops, known as aptamers, protruding from their surfaces at defined positions. By incorporating two different aptamers into the DNA tiles, arrays comprising alternating periodic lines of two different proteins were formed. To produce arbitrary patterns, Yan and colleagues made rigid scaffolds — with a technique referred to as 'DNA origami' — by folding one long DNA strand with the help of more than 200 shorter ones, some of which contained aptamer sequences. With this approach, proteins were assembled in an 'S' shape, but, in principle, any geometric pattern is possible.

The flexibility of linear DNA templates often leads to unwanted sandwich structures formed between adjacent proteins, but the use of rigid two-dimensional scaffolds prevents this from occuring. Moreover, the protein-binding properties of each aptamer are retained in the templates, leading to highly specific assembly of spatially addressable multiprotein arrays.