'Molecular printboard' technique builds protein biochips with unprecedented control over binding specificity, strength, and orientation

Chemists in the Netherlands have created nanoscale structures that can immobilize proteins with exquisite control over specificity, strength and orientation. The researchers hope their method will bring integrated biochips, which might combine any protein function with electronic or sensory elements, a step closer. 

Jurriaan Huskens at the MESA+ Institute for Nanotechnology at Enschede, and colleagues, used the so-called molecular printboard technique that Huskens had previously developed. The technique combines top-down approaches to nanotechnology, such as lithography, with bottom-up approaches like self-assembly and supramolecular chemistry.1

The printboard technique, so named for its parallels with the motherboard of a computer (comprising a printed circuit with additional functionalities plugged in), involves printing a patterned layer of cyclodextrins onto a surface of gold or glass. Using the strong affinity that cyclodextrins show towards certain guest molecules, researchers can then add further layers of building blocks tagged with such molecules. 

To extend the application range to proteins, Huskens’ team has now introduced a new type of linker, hexa (ethylene glycol) mono (adamantyl ether). They found that this molecule forms a dynamic second layer on top of the cyclodextrin, which can prevent unwanted effects like non-specific binding of protein, but can make way for the ’right’ proteins to be bound to the surface in the desired orientation. This is achieved via a specific linker that also contains an adamantane group, and thus competes with the glycol layer and binds directly to the cyclodextrin.2

Correct orientation is vital - to see an enzyme in action, for example, the enzyme must have its active site exposed and not stuck to the board. Researchers could arrange multiple functionalities (several steps in an enzymatic reaction path, say) in a group, to monitor different stages of the reaction at once. Or they could combine proteins with non-biological functional units, such as transistors or quantum dots, and perhaps use an electronic signal to switch an enzyme on. Conversely they could detect a receptor-binding event via the electronic output. 

Roberto Cao, who also uses cyclodextrins for nanotechnology in his research at the University of Havana, Cuba, welcomed the new development. ’This linker provides a loose packing of the protein and, on the other hand, its hydrophilicity offers a well-hydrated environment,’ Cao told Chemistry World. ’Both factors achieve a highly stable organized immobilization of proteins with complete control over their orientation on the surface,’ he said. ’It constitutes an important step forward in the preparation of protein biochips.’

Michael Gross

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Link to journal article

Writing with molecules on molecular printboardsOlga Crespo-Biel, Bart Jan Ravoo, Jurriaan Huskens and David N. Reinhoudt,?Dalton Trans., 2006, 2737DOI:10.1039/b517699a