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Cellular microfabrication: Observing intercellular interactions using lithographically-defined DNA capture sequences

Onoe Hiroaki; Hsiao Sonny C; Douglas Erik S; Gartner Zev J; Bertozzi Carolyn R; Francis Matthew B; Mathies Richard A*
Engineering Village
University of California; 1; university of california; United States

摘要

Previous reports have shown that synthetic DNA strands can be attached to the plasma membrane of living cells to equip them with artificial adhesion "receptors" that bind to complementary strands extending from material surfaces. This approach is compatible with a wide range of cell types, offers excellent capture efficiency, and can potentially be used to create complex multicellular arrangements through the use of multiple capture sequences. In this work, we apply an aluminum "lift off" lithography method to allow the efficient generation of complex patterns comprising different DNA sequences. The resulting surfaces are then demonstrated to be able to capture up to three distinct types of living cells in specific locations. The utility of this approach is demonstrated through the observation of patterned cells as they communicate by diffusion-based paracrine signaling. It is anticipated that the ability of this technique to create virtually any type of 2D heterogeneous cell pattern should prove highly useful for the examination of key questions in cell signaling, including stem cell differentiation and cancer metastasis.

关键词

Cancer metastasis Capture efficiency Cell patterns Cell signaling Cell types Complementary strand Complex pattern Intercellular interactions Living cell Material surface Paracrine Specific location Stem cell differentiation Synthetic DNA strands