The dynamic attachment and detachment of cells to and from their extracellular milieu regulates cell motility and is critical for embryonic development, the inflammatory immune response, wound repair, and metastasis of cancerous cells. The overall goal of this project is to determine the global dynamics of cell contraction, focal adhesion disassembly, and cytoskeleton reorganization after detachment from a surface, and, in addition, to decipher the molecular mechanisms that drives and regulates this process. Our motivation is that the current state-of-the-art to study cell detachment involves bulk depolymerization and repolymerization of microtubules by nocadozole, a non-specific pharmacological approach that does not allow for spatially controlled release of focal adhesions at the sub-cellular level. The technological challenge is to develop a tool to study and control cell detachment that will allow release of focal adhesions over sub-cellular regions in a spatially and temporally controlled manner. In preliminary work we have demonstrated the feasibility of programmed sub-cellular release in addressing important questions related to cell detachment.
Narrative Cell detachment is central to processes from migration to metastasis. The proposed research will develop a new tool to measure cell detachment and allow new insight into the molecular mechanisms that drive and regulate cell detachment, focal adhesion disassembly, and cytoskeleton reorganization.
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| Wildt, Bridget; Wirtz, Denis; Searson, Peter C (2009) Programmed subcellular release for studying the dynamics of cell detachment. Nat Methods 6:211-3 |
