General Research Interests
Our research focuses on synthesis of biologically active
nanostructures and their applications to biological imaging,
and a major focus is synthesizing nanoparticles with novel optical
properties. We have developed caged quantum dots, which are non-luminescent
under typical microscopic illumination but can be activated with
stronger pulses of UV light. These nanoparticles are hybrids
of hard and soft materials, and their unique optical 
properties
arise from the interaction between a classic organic caging group
and a semiconducting QD. These nanoparticles endow quantum dots
with one of the most useful properties of bioimaging probes—the
ability to be switched on with light—and promise to be
valuable in a variety of applications, including superresolution
imaging, time-resolved live cell imaging, and selective spatial
activation for studying protein trafficking and polarized cells.
We are developing a second type of nanoparticle (in collaboration
with Delia Milliron of the Inorganic Facility and Jim Schuck
of Imaging) with interesting optical properties for bioimaging,
lanthanide-doped upconverting nanoparticles (UCNPs). These
particles absorb 2 photons in the near infrared (nIR) and
emit at shorter wavelengths in the visible or nIR. This property
will be exceptionally valuable for bioimaging: compared to
visible or UV, nIR radiation is less 
damaging
to cells, produces much less autofluorescent background,
and scatters less, allowing deeper tissue penetration or
even whole animal imaging. We have developed a synthesis
of monodisperse UCNPs in the desired size regime and a simple
procedure for transferring them to water. With these, we
have recorded the first single molecule images of UCNPs,
showing that they do not blink (as QDs and many organic probes
do) and that they posses remarkable photostability, resisting
photobleaching long after organics and QDs do. We are finding
other interesting spectral characteristics at the single-molecule
level, and we are currently exploring UCNPs for cellular
imaging experiments, as well as other advanced imaging applications.
A third project is to develop genetically encoded fluorescent
nanostructures as protein imaging tags. We are using phage
panning to find peptide sequences that bind to novel nIR
organic fluorophores. Fusion of these fluorophore-binding
sequences to proteins of interest using standard molecular
biology techniques will provide a means of fluorescently
labeling intracellular proteins in live cells. For this project,
we have synthesized several new nIR dyes, two of which show
exceptional brightness, and we are identifying phage sequences
that bind to these dyes. The peptides will be structurally
characterized in complex with the dyes and then optimized
into high-affinity sequences that can be used as to form
nano-fluorescent proteins in cells.
Selected publications:
S. Wu, G. Han, D.J. Milliron, S. Aloni, V. Altoe, D.V. Talapin,
B.E. Cohen, P.J. Schuck. Non-blinking and photostable upconverted
luminescence from single lanthanide-doped nanocrystals. PNAS,
in press.
G. Han, T. Mokari, C. Ajo-Franklin, B.E. Cohen. Caged quantum
dots. J. Am. Chem. Soc. 130, 15811-15813 (2008). http://pubs.acs.org/doi/full/10.1021/ja804948s
J.S. Salafsky, B.E. Cohen. A second-harmonic-active unnatural
amino acid as a structural probe of biomolecules on surfaces.
J. Phys. Chem. B 112, 15103–15107 (2008). http://pubs.acs.org/doi/full/10.1021/jp803703m
P. Abbyad, X. Shi, W. Childs, T.B. McAnaney, B.E Cohen, and S.G.
Boxer. Measurement of solvation responses at multiple sites in
a globular protein. J. Phys. Chem. B 111, 8269-8276 (2007). http://pubs.acs.org/doi/full/10.1021/jp0709104
B.E. Cohen, A. Pralle, X. Yao, G. Swaminath, C. Gandhi, Y.N.
Jan, B.K. Kobilka, E.Y. Isacoff, E.Y., and L.Y. Jan. A fluorescent
probe designed for studying protein conformational change. PNAS
102, 965-970 (2005). http://www.pnas.org/content/102/4/965.full
B.E. Cohen, T.B. McAnaney, E.S. Park, Y.N. Jan, S.G. Boxer, and
L.Y. Jan. Probing protein electrostatics with a synthetic fluorescent
amino acid. Science 296, 1700-1703 (2002). http://www.sciencemag.org/cgi/content/full/296/5573/1700
MSD Research Projects:
