Nanostructures have received extensive attention for their promising applications in electronics, photonics, andinformation storage. I believe these minuscule structures also hold great potential for advancing biomedicalresearch. In particular, I have always wanted to harness the power of nanostructures to radically change the waycell behavior is probed and regulated. Here I propose to develop the next generation of toolset for studying andmanipulating cell activity by bringing together three classes of complementary nanostructures: gold nanocagescapable of absorbing near infrared light and effectively converting it to heat; smart polymers capable of changingconformation in response to small variation in temperature; and enzymes. The stimuli-responsive polymer will becovalently attached to a specific position near the active site of the enzyme; the resultant unit will be conjugatedto the surface of gold nanocage. When the nanocage is struck with a pulsed laser, the polymer conformation willbe quickly and reversibly switched between the extended and collapsed states, turning on and off the enzyme. Todemonstrate the biological importance of such hybrid nanostructures, I will initially apply them to manipulate cellbehavior such as apoptosis. A variety of trapping techniques will also be adapted to control the spatial position ofthe hybrid nanostructure inside and outside an individual cell. For the first time, I will be able to ascertain theminimum number of active enzymes required to initiate apoptosis, and whether and how the spatial location of theenzyme affects apoptosis signaling. Once it has been demonstrated for apoptosis, the concept will be extended todevelop 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 otherbioimaging techniques under development, and will find broad use in studying complex biological systems.
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