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.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
5DP1OD000798-06
Application #
7911808
Study Section
Special Emphasis Panel (ZGM1-NDPA-G (P2))
Program Officer
Jones, Warren
Project Start
2006-09-28
Project End
2011-12-31
Budget Start
2010-08-01
Budget End
2011-12-31
Support Year
6
Fiscal Year
2010
Total Cost
$2
Indirect Cost
Name
Washington University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Zhu, Chunlei; Pongkitwitoon, Suphannee; Qiu, Jichuan et al. (2018) Design and Fabrication of a Hierarchically Structured Scaffold for Tendon-to-Bone Repair. Adv Mater 30:e1707306
Xue, Jiajia; Xie, Jingwei; Liu, Wenying et al. (2017) Electrospun Nanofibers: New Concepts, Materials, and Applications. Acc Chem Res 50:1976-1987
Zhang, Yu Shrike; Zhu, Chunlei; Xia, Younan (2017) Inverse Opal Scaffolds and Their Biomedical Applications. Adv Mater 29:
Zhang, Yu Shrike; Wang, Lihong V; Xia, Younan (2016) Seeing Through the Surface: Non-invasive Characterization of Biomaterial-Tissue Interactions Using Photoacoustic Microscopy. Ann Biomed Eng 44:649-66
Pang, Bo; Yang, Xuan; Xia, Younan (2016) Putting gold nanocages to work for optical imaging, controlled release and cancer theranostics. Nanomedicine (Lond) 11:1715-28
Lipner, Justin; Shen, Hua; Cavinatto, Leonardo et al. (2015) In Vivo Evaluation of Adipose-Derived Stromal Cells Delivered with a Nanofiber Scaffold for Tendon-to-Bone Repair. Tissue Eng Part A 21:2766-74
Zhang, Yu Shrike; Xia, Younan (2015) Multiple facets for extracellular matrix mimicking in regenerative medicine. Nanomedicine (Lond) 10:689-92
Yang, Xuan; Yang, Miaoxin; Pang, Bo et al. (2015) Gold Nanomaterials at Work in Biomedicine. Chem Rev 115:10410-88
Zhang, Yu Shrike; Cai, Xin; Yao, Junjie et al. (2014) Non-invasive and in situ characterization of the degradation of biomaterial scaffolds by volumetric photoacoustic microscopy. Angew Chem Int Ed Engl 53:184-8
Zhang, Yu Shrike; Yao, Junjie; Wang, Lihong V et al. (2014) Fabrication of Cell Patches Using Biodegradable Scaffolds with a Hexagonal Array of Interconnected Pores (SHAIPs). Polymer (Guildf) 55:445-452

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