SCIENTISTS CREATE NEW PROTEIN BASED MATERIAL WITH SOME NERVE

Scientists at the University of California, Berkeley, have taken proteins from nerve cells and used them to create a "smart" material that is extremely sensitive to its environment. This marriage of materials science and biology could give birth to a flexible, sensitive coating that is easy and cheap to manufacture in large quantities.

The work, to be published Oct. 14, in the journal Nature Communications, could lead to new types of biological sensors, flow valves and controlled drug release systems, the researchers said. Biomedical applications include microfluidic devices that can handle and process very small volumes of liquid, such as samples of saliva or blood, for diagnostics.

"This work represents a unique convergence of the fields of biomimetic materials, biomolecular engineering and synthetic biology," said principal investigator Dr. Sanjay Kumar, UC Berkeley associate professor of bioengineering. "We created a new class of smart, protein-based materials whose structural principles are inspired by networks found in living cells."

Kumar's research team set out to create a biological version of a synthetic coating used in everyday liquid products, such as paint and liquid cosmetics, to keep small particles from clumping together. The synthetic coatings are often called polymer brushes because of their bristle-like appearance when attached to the particle surface.

To create the biological equivalent of a polymer brush, the researchers turned to neurofilaments, pipe cleaner-shaped proteins found in nerve cells. By acting as tiny, cylindrical polymer brushes, neurofilaments collectively assemble into a structural network that helps keep one end of the nerve cell propped open so that it can conduct electrical signals.

"We co-opted this protein and turned it into a polymer brush by cloning a portion of a gene that encodes one of the neurofilament bristles, re-engineering it such that we could attach the resulting protein to surfaces in a precise and oriented way, and then expressing the gene in bacteria to produce the protein in large, pure quantities," said Kumar. "We showed that our 'protein brush' had all the key properties of synthetic brushes, plus a number of advantages."

Kumar noted that neurofilaments are good candidates for protein brushes because they are intrinsically disordered proteins, so named because they don't have a fixed 3-D shape. The size and chemical sequence of these hair-like proteins are far easier to control when compared with their synthetic counterparts.

"In biology, precision is critical," said Kumar. "Proteins are generally synthesized with the exact same sequence every time; the length and biochemical order of the protein sequence affects all of its properties, including structure and the ability to bind to other molecules and catalyze biochemical reactions. This kind of sequence precision is difficult if not impossible to achieve in the laboratory using the tools of chemical synthesis. By harnessing the precision of biology and letting the bacterial cell do all the work for us, we were able to control the exact length and sequence of the bristles of our protein brush."

The researchers showed that the protein brushes could be grafted onto surfaces, and that they dramatically expand and collapse in reaction to changes in acidity and salinity. Materials that are environmentally sensitive in this way are often referred to as "smart" materials because of their ability to adaptively respond to specific stimuli.

PROTEIN REGULATES BURNING OF BODY FAT

Muscle movements generate body heat. However, body heat can also be generated in another way: body fat contains a small number of brown adipose cells -- special fat cells that can generate heat without muscle activity. They do this using a protein known as UCP1 that enables babies or hibernating animals to keep warm without shivering. A research team at the University of Veterinary Medicine (Vetmeduni Vienna) has found that a specific chemical compound, an aldehyde, can activate UCP1 under certain conditions, and that could also trigger fat burning. The data were published in the journal PLoS One

The uncoupling Protein 1 (UCP1) is found exclusively in brown adipose tissue. Until some years ago it was thought that only babies and hibernating animals had brown adipose tissue, but since then it also has been found in adults, so UCP1 could be useful in the fight against obesity. "If we can find out how to regulate this protein, we might also find a way to trigger fat burning in the body," explains biophysicist Elena Pohl from the Unit of Physiology and Biophysics at the Vetmeduni Vienna.

UCP1 burns energy

UCP1 is located in the membrane of mitochondria, the power plants that fuel every single cell in the body. Cells that require a lot of energy, such as muscle cells, contain many mitochondria. But brown adipose tissue contains even more mitochondria than muscle tissue. In fact, it is the mitochondria that are responsible for the brown colour of this form of adipose tissue. Regular adipose tissue, which is the majority, is white. UCP1 in mitochondria uses the cell's energy to produce heat. If UCP1 is 'turned off' in mice, the animals will freeze. Hibernating animals would not survive the winter if they did not have this protein.

Researchers aim to regulate UCP1

Elena Pohl and her research group are trying to find a way to regulate UCP1. In a project funded by the FWF, they have tested different substances reported to activate UCP1, under them also reactive aldehyde 4-hydroxy-2-nonenal (HNE).Using an artificial cell membrane containing UCP1, the researchers were able to detect the activity of the protein by measuring the electrical conductivity on the membrane. The researchers dripped HNE onto the membrane and found that UCP1 can be activated by HNE only if combined with fatty acids. "In this model, all the 'players' are known so we could determine clearly whether the substance influences the protein directly or not. The discovery helps to improve our understanding of the mechanisms that regulate UCP1 and may even lead us to a way to burn body fat," explains co-author Olga Jovanovic.

Reducing free radicals

Free radicals play an important role in many biological processes, but they also cause cellular damage and play a crucial role in the pathogenesis of various diseases such as cancer, atherosclerosis and Alzheimer's disease. The research team has also shown that HNE, combined with fatty acids, also has the potential to minimize these damaging free radicals by reducing the membrane potential. "We want to elucidate the molecular mechanisms of UCP. We are still examining various aldehydes and other UCPs. There are five different UCPs and all their functions are not yet fully understood. We hope that our work will contribute to the development of therapies for various diseases."

Drugs in the battle against obesity

In the 1930s, a substance similar to UCP1 was developed that seemed to promise an easy way of losing weight. The substance was called 2,4-dinitrophenol and, like UCP1, it worked as an uncoupler in the mitochondria of cells. Taken in the right amounts, the drug accelerates the human metabolism by up to 50 percent. However, in some cases it caused serious or even lethal side effects and had to be withdrawn from the market. "If we are able to regulate UCP1 in a controlled way, it might be different story," says Pohl.