Remote Control of Cells
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During natural processes of tissue development and maintenance, cells exhibit complex behaviors that organize them into functional assemblies. The ability to intervene in these processes and take control of cell behavior enables creation of engineered tissues as well as basic studies of cell biology that dissect processes of tissue growth. We are developing technology to control cells by harnessing the chemical signals that naturally direct tissue growth. These growth factors are polypeptides that influence a wide variety of cellular behaviors. They diffuse within the cellular medium, and spatial patterns within tissues are created by gradients of their concentrations. To emulate the spatial aspect of growth factor function in tissue development and maintenance, we are engineering growth factors that are inactive until “turned on” with light. In this way, concentration gradients can be generated with the spatial precision with which light can be directed. As a first test of this approach, we have chemically synthesized epidermal growth factor in which a critical side chain is “caged” with a photoremovable group. Epidermal growth factor stimulates proliferation and directional migration of cells, and photolysis of the engineered polypeptide affords maximal activity at concentrations where the caged factor is inactive. Spatially resolved photolysis of the factor using a Digital Micromirror Array for illumination results in spatial patterning of cells. This system will be useful for ex vivo tissue engineering and for investigating the interactions of cells with their matrix and the role of growth factor gradients in biological pattern formation. |
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MetroCon 2007 |
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“Innovating for Society” |
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Biotechnologies |
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Kevin Luebke received a Bachelor of Science degree with highest distinction and honors from Purdue University in 1986. He received a Ph.D in chemistry from the California Institute of technology in 1992, studying molecular recognition of nucleic acids. He then did post-doctoral research at the University of California Berkeley, carrying out biophysical studies on RNA conformation. He was a Senior Scientist at Hewlett-Packard Laboratories from 1996 to 1998, working on synthesis of DNA arrays with ink-jet printing. From there, he joined the faculty of Internal Medicine at the University of Texas Southwestern Medical Center, where he has been working in the areas of tissue engineering, chemical genetics, and small molecule-RNA interactions. |
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