NIH Director's Pioneer Award

Washington University, Saint Louis MO

Investigators

Linked publications & trials

Abstract

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