Extracellular mechanical signals (EMS) can regulate nuclear morphology and chromatin dynamics via the physical link from focal adhesions to chromatin via the cytoskeleton, linker proteins on the nuclear envelope and the nuclear lamina. However, how such force transmission from cytoskeleton to the nucleus is regulated by different EMS and their effect on nuclear and chromatin dynamics is not well understood. In the first project, using micropillar substrates and correlation analysis techniques, we measured the time scale at which nuclear and chromatin dynamics respond to traction forces at cell periphery in unperturbed cells. In the second project, using nuclear envelope fluctuations and heterochromatin dynamics as readout, we characterized how cytoskeletal forces alter depending on the EMS provided by micropatterned substrates. In the third project, we developed a technique to quantify chromatin dynamics and used it to study the effect of cytoskeletal perturbations on chromatin dynamics and binding of transcription regulators. Taken together, this work provides a quantitative understanding of the coupling between cellular mechanotransduction and nuclear and chromatin plasticity.
|School:||National University of Singapore (Singapore)|
|School Location:||Republic of Singapore|
|Source:||DAI-B 77/06(E), Dissertation Abstracts International|
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