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Modifying the shapes of cells to influence function
  
By
Edward R. Winstead


 

Scientists have developed specialized glass surfaces for growing cells that allow them to control and modify the shapes of cells and their nuclei. By manipulating the shapes of cell nuclei, the researchers altered the expression of specific genes and accelerated the maturation of young 'undifferentiated' cells into 'mature' bone cells. The glass surfaces could potentially be placed on synthetic implants as a way to promote the development of certain cell types and facilitate the integration of body implants.


Images of cells on pattered adhesive islands. View larger

Researchers have long known that the shape, or geometry, of cells influences what goes on inside a cell. The wrong shape can prevent proteins from being produced, promote cell death (apoptosis), or lead to tumors. In the new study, Kevin E. Healy, of the University of California, Berkeley, and colleagues refine this concept. They show that certain changes in gene and protein expression are related not only to cell shape but, more precisely, to the shape of the cell nucleus.

The researchers arrayed rat cells derived from bone tissue on glass slides containing 12,000 binding domains or 'islands'. Each cell adopts the shape of a binding island, a process that also affects the shape of the nucleus. The researchers then manipulated the cells, creating a range of geometric shapes and sizes, and monitored the development of the cells over time. Different nuclear shapes were associated with significant changes in the expression of certain genes related to bone development, according to findings published in Proceedings of the National Academy of Sciences.

The key to exploiting the technology for medical and research purposes is being able to produce the changes in gene and protein expression that lead to the desired cell types. Two potential uses for the surface technology are implant operations and drug development.

With implants, the glass surfaces could be used to influence the development of cells in the body that come into contact with the implant. The specialized surface can in theory speed the maturation of adult cells necessary for integrating synthetic devices such as replacement joints, dental implants, or cardiovascular grafts or stents.

"This technology gives us the opportunity to have better control over the behavior of cells that come into contact with the surface of the implant," says Healy. "If you're trying to speed the natural integration of a total hip replacement into the body, then what you want are cells that are specific to the types of tissue that will line the implant."

In drug development, researchers need high-throughput methods for screening compounds against cells to determine their therapeutic effects. The specialized surfaces could in theory reduce the time it takes for cultured cells to develop into the cell phenotype needed for a particular experiment. The growth and differentiation process for certain cells can take up to two weeks; the new approach could significantly reduce this period.

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Thomas, C.H. et al. Engineering gene expression and protein synthesis by modulation of nuclear shape. Proc Natl Acad Sci USA 99, 1972-1977 (February 19, 2002).
 

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