NIH Director's Pioneer Award

点击翻译按钮获取中文摘要

Nanostructures have received extensive attention for their promising applications in electronics, photonics, and information storage. I believe these minuscule structures also hold great potential for advancing biomedical research. In particular, I have always wanted to harness the power of nanostructures to radically change the way cell behavior is probed and regulated. Here I propose to develop the next generation of toolset for studying and manipulating cell activity by bringing together three classes of complementary nanostructures: gold nanocages capable of absorbing near infrared light and effectively converting it to heat; smart polymers capable of changing conformation in response to small variation in temperature; and enzymes. The stimuli-responsive polymer will be covalently attached to a specific position near the active site of the enzyme; the resultant unit will be conjugated to the surface of gold nanocage. When the nanocage is struck with a pulsed laser, the polymer conformation will be quickly and reversibly switched between the extended and collapsed states, turning on and off the enzyme. To demonstrate the biological importance of such hybrid nanostructures, I will initially apply them to manipulate cell behavior such as apoptosis. A variety of trapping techniques will also be adapted to control the spatial position of the hybrid nanostructure inside and outside an individual cell. For the first time, I will be able to ascertain the minimum number of active enzymes required to initiate apoptosis, and whether and how the spatial location of the enzyme affects apoptosis signaling. Once it has been demonstrated for apoptosis, the concept will be extended to develop similar hybrid nanostructures for reading and controlling other cellular processes and signaling pathways. Such a toolset based on spatially and temporally addressable nanostructures is complementary to many other bioimaging techniques under development, and will find broad use in studying complex biological systems.