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'Plastic' proteins aid drug discovery

By Kwok Wan, 24-Apr-2008

Related topics: Processing

Researchers have created a hybrid gel that can reacts to changes in acidity and temperature by turning green. The gel, made from a combination of synthetic polymers and proteins, could be used as sensors, nanomachine parts or drug discovery systems.

Aaron P Esser-Kahn and Matthew B Francis, scientists at the University of California, Berkeley, have been able to fuse the specific biological functions of proteins with the advantageous bulk and processing properties of plastic. The hybrid material also has other special properties, like being biodegradable as it can be eaten by proteases (enzymes that dissolve proteins).

 

 

 

These kinds of hydrogels and ones that are responsive to specific molecules, such as glucose or antigens, can be used as biosensors and utilised for drug discovery because 3D structures are needed needed for cells proliferation because they have larger surface for cell attachment.

 

 

 

It is important to create an environment suitable for cells as close as possible to natural ones. The conventional static culture method cannot supply enough oxygen and nutrition to cells in the 3D structures and exclude cell wastes for their proliferation and differentiation.

 

 

 

The problem of environment and culture design to facilitate and enhance the viability and functions of cells could be solved by the design of 3D hydrogels which are sufficient for survival of large numbers of cells for extended periods of time through diffusion of nutrients, bioactive factors, and oxygen.

 

 

 

In the past, other methods of producing hybrid materials relied on very specific coupling techniques. These techniques cannot be used for some protein side-chains, but according to Esser-Kahn and Francis their new method should be suitable for any protein.

 

 

 

Their technique was to make the coupling occur at both ends of the protein chain, one amino acid group and one carboxylic acid group, and this is the same for all proteins. To begin with, two parallel but indepedent reactions are used to activate the two ends of the chain. These are then attached to chemical points on the polymer.

 

 

 

The proteins therefore cross link the individual polymer chains and creates a 3D network, forming the hydrogel. This solid, jelly-like mass is much like a contact lens and is made of mainly water and contains the polymer network.

 

 

 

The team also chose proteins that fluoresced green to cross link the polymers meaning the whole gel fluoresces green. A property of the fluorescence is that it is pH dependent and therefore the gel reacts to changes in pH. Raising the temperature also causes the gel to shrink, as the heat quenches the fluorescence.