Hung-Jen Wu Research Lab
Chemical Engineering, Texas A&M University
Research
1.
Multivalent lectin binding & bacterial adhesion to host cell membranes
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Figure 1 Multivalent binding on cell membranes |
Glycans
expressed on cell surfaces mediate a wide range of biological processes, such
as pathogen (e.g. bacterial, viral) and exotoxin adhesion to host cells.
Interestingly, a single glycan-protein interaction is often weak; most proteins
bind to glycans via multivalent interactions, in which multiple binding domains
in a single protein simultaneously interact with multiple glycan molecules.
Glycan receptors on cell membranes are often mobile; glycans attached to lipids
or membrane proteins can freely diffuse and rotate on 2D fluidic cell
membranes, self-organizing to reach multivalent interactions with a protein.
Such multivalency leads to higher binding avidity and specificity, and is one
of the major recognition principles in many biological systems.
We
recently monitored the hetero-multivalent
binding process of Cholera Toxin Subunit B (CTB) (i.e. a
CTB simultaneously binding to two or more different types of glycolipid
receptors). Surprisingly, when a very weak receptor (e.g. GM2) was mixed with
the strong binding receptor (e.g. GM1), GM1 activated the interactions between
CTB and GM2, enhancing the overall CTB attachment. We demonstrated that the
activation of low-affinity receptors was mediated via
a simple chemistry mechanism, Reduction
of Dimensionality (RD). (see
Figure 2) After CTB attaching to the first receptor, the subsequent binding
events are confined in a two dimensional membrane
surface. Due to the reduced dimensionality of diffusion, the effective concentrations
of weak receptors dramatically increase for the subsequent binding events;
therefore, a weak receptor can contribute to CTB binding.
The RD mechanism
strongly depends on cell membrane dynamics. This presents an issue to
conventional ligand-receptor screening assays (e.g. microarray technology,
ELISA, etc.) because these tools that often immobilize
receptors on solid surfaces miss the inherent membrane dynamics. To date, no
theoretical model is available to describe the fundamental RD process. My research
group is developing novel sensing technologies and computation tools to
investigate the RD mechanism and understand the influence of
hetero-multivalency in the pathogenesis of bacteria (e.g. Pseudomonas aeruginosa and Mycobacterium tuberculosis).
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2.
Multifunctional nanomaterials for biosensing
My research group focuses on developing
highly structured nanomaterials for biosening. We
have established the novel instruments to quantitatively
explore various biological processes, including nanocube-based lipid
bilayer array, multiplexing chemical and biological Raman sensors, and Nanotrap for infectious disease screening.
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Figure 3 Nanocube-based
Lipid Bilayer Array. Silica-coated silver nanocubes are covered
by supported fluidic lipid bilayers where receptors are presented. Binding
kinetics were detected by monitoring absorption spectra with standard microplate
reader |
3.
Quantitative surface enhanced Raman spectroscopy (SERS)
Figure 4. Measuring Reaction
Kinetics with Quantitative SERS Using Ag@AuNC
Substrate
4. Role
of microvesicle/exosome in infectious diseases
Figure 5. Isolation of
Exosome Using Microfluidic Device