Take a neural stem cell in the brain: Whether this cell remains a stem cell or differentiates into a fully formed brain cell is ultimately determined by a complex set of molecular messages the cell receives from countless neighbors. Understanding these messages is key for scientists hoping to harness these stem cells to treat neurological conditions like Alzheimer's or Parkinson's.
With the help of photolithography and a creative use of programmable DNA, University of California, Berkeley, researchers have created a new technique that can rapidly "print" two-dimensional arrays of cells and proteins that mimic a wide variety of cellular environments in the body - be it the brain tissue surrounding a neural stem cell, the lining of the intestine or liver or the cellular configuration inside a tumor.
University of California, Berkeley, researchers have created a new technique that utilizes photolithography and programmable DNA to rapidly "print" two-dimensional arrays of cells and proteins that mimic a wide variety of cellular environments in the body.
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This technique could help scientists develop a better understanding of the complex cell-to-cell messaging that dictates a cell's final fate, from neural stem cell differentiating into a brain cell to a tumor cell with the potential to metastasize to an embryonic stem cell becoming an organ cell.
"What's really powerful about this platform is you can create in vitro tissues that capture the spatial organization of cells in the body, from the intestinal lining of your digestive tract to the arrangements of different cell types in the liver," said Olivia Scheideler, who completed the research as a graduate student at Berkeley. "I think you could apply this technique to recreate any tissue where you want to explore how cellular interactions contribute to tissue function."
"Essentially, what this technique allows us to do is pattern different kinds of conditions in one shot and in a high-throughput manner," said Lydia Sohn, Chancellor's Prof. of Mechanical Engineering at UC Berkeley and senior author of the paper. "It provides a whole range of options for what you could study, because it's so flexible. You can pattern many different kinds of cells or proteins."
In the new technique, each cell or protein is tethered to a substrate with a short string of DNA. While similar methods have been developed that attach tethered cells or proteins one by one, the new technique takes advantage of a patterning process called photolithography to attach, or print, each type of cell protein in one quick batch, greatly speeding up the process.
"It's like color laser printing, where you print one color and then print another," Sohn said.
Like photography, photolithography works by exposing a coated surface or substrate to a pattern of light, which initiates a chemical reaction that dissolves the coating in the illuminated areas, leaving a templated substrate. In the new technique, the substrate is then bathed in strands of single-sided DNA, whose ends have been chemically altered to firmly latch on where the coating has been dissolved.
Each single-sided DNA strand is programmed have a specific sequence of the nucleotides adenine (A), thymine (T), guanine (G) and cytosine (C). Single-sided DNA strands with the complementary nucleotide sequence are embedded or attached to cells or proteins of interest.
Finally, the surface is washed with a mixture of cells or proteins attached to the complementary strands of single-sided DNA, which bond with the single-sided DNA already attached to the surface to form double-helix "tethers."
"All the cells and proteins attach exactly where they should be because of the DNA programming," Sohn said.
By repeating the process, up to 10 different kinds of cells or proteins can be tethered to the surface in an arbitrary pattern.
To demonstrate one of the many applications of the technique, Scheideler and co-author David Schaffer, Hubbard Howe Jr. Distinguished Prof. of Biochemical Engineering at UC Berkeley, used the platform to study the chemical signaling that cues neural stem cells to differentiate into mature cells.
MEDICA-tradefair.com; Source: University of California – Berkeley