NEW TECHNIQUE DEVELOPED FOR ATTACHING BIOLOGICAL CELLS TO NON-BIOLOGICAL SURFACES

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NEW TECHNIQUE DEVELOPED FOR ATTACHING BIOLOGICAL CELLS TO NON-BIOLOGICAL SURFACES
06 July 2006 - DOE/Lawrence Berkeley National Lab

A new technique in which single strands of synthetic DNA are used to firmly fasten biological cells to non-biological surfaces has been developed by researchers with the Lawrence Berkeley National Laboratory and the University of California at Berkeley. This technique holds promise for a wide variety of applications, including biosensors, drug-screening technologies, the growing of artificial tissues and the design of neural networks.

"Just as DNA chips revolutionized genome analysis, we hope to make cell chips (self-assembled arrays of cells on a thumbnail-sized chip) using our DNA-based cell adhesion strategy," said Ravi Chandra, a researcher affiliated with Berkeley Lab's Physical Biosciences Division and UC Berkeley's Chemistry Department. "Cell chips could be used as biosensors for detecting the presence of pathogens, or for drug screening, just to name of a few of the many possibilities."

Chandra is the lead author of a paper that appears in the latest issue of the international chemistry journal Angewandte Chemie. The other authors are Erik Douglas, Richard Mathies, Carolyn Bertozzi and Matthew Francis. The paper is entitled: Programmable Cell Adhesion Encoded by DNA Hybridization.

Many of the vast assortment of biological cells are naturally sticky, a property that enables individual cells to adhere to other cells and non-cellular components, which in turn enables them to assemble into different types of tissue, or carry out functions critical to an organism's health and well-being. Cell adhesion is now being used to incorporate biological cells into simple devices, but is expected to be important for the future production of complex nanotechnology devices.

To date, researchers have been attaching cells to surfaces using the array of cell adhesion proteins that Nature has provided, especially the proteins known as integrins. A surface will be laid out in a desired pattern with chemical handles called "ligands" to which the integrin-coated cells will bind. However, integrins are cell adhesion generalists, just about all of the different types of cells will stick to the same ligands. This makes integrin-coated cells ill-suited for applications that require precise patterns of multiple cell types.

The authors behind the Angewandte Chemie paper have solved the problem with the creation of a highly selective cell adhesion system that uses single-strands of synthetic DNA to fasten the cells to a surface. This enables different types of cells to be selectively targeted and attached to specific locations on a surface based on the nucleotide sequences of the single-stranded DNA.

"We can pattern a surface with single-stranded DNA containing a specific nucleotide sequence, then coat cells with single-stranded DNA that contains a complementary sequence," said Chandra, who is a member of both the Francis and Bertozzi research groups. Francis holds a joint appointment with Berkeley Lab's Materials Sciences Division and the UC Berkeley Chemistry Department, and is an expert in linking organic molecules to nanoparticles to create hybrid structures. Bertozzi, who also holds a joint appointment with Berkeley Lab and UC Berkeley, is a leading authority on cell surface interactions. She is also a member of the Howard Hughes Medical Institute.

"Since the cells will adhere to the surface at locations where the complementary nucleotide sequences match, we can program cell adhesion events with a virtually unlimited number of possible coding options," said Chandra. "The DNA effectively serves as a molecular barcode on the surface of living cells."

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About: DOE/Lawrence Berkeley National Lab
Lawrence Berkeley National Laboratory (Berkeley Lab) has been a leader in science and engineering research for more than 70 years. Located on a 200 acre site in the hills above the Berkeley campus of the University of California, overlooking the San Francisco Bay, Berkeley Lab is a US Department of Energy (DOE) National Laboratory managed by the University of California. It has an annual budget of nearly $480 million (FY2002) and employs a staff of about 3,900, including more than a thousand students.

Berkeley Lab conducts unclassified research across a wide range of scientific disciplines with key efforts in fundamental studies of the universe; quantitative biology; nanoscience; new energy systems and environmental solutions; and the use of integrated computing as a tool for discovery. It is organized into 17 scientific divisions and hosts four DOE national user facilities. Details on Berkeley Lab’s divisions and user facilities can be viewed here.

The Lab was founded in 1931 by Ernest Orlando Lawrence, winner of the 1939 Nobel Prize in physics for his invention of the cyclotron, a circular particle accelerator that opened the door to high-energy physics. It was Lawrence’s belief that scientific research is best done through teams of individuals with different fields of expertise, working together. His teamwork concept is a Berkeley Lab legacy that has yielded rich dividends in basic knowledge and applied technology, and a profusion of awards, including nine Nobel Prizes -- five in physics and four in chemistry.

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