Creating synthetic antibodies
Synthetic polymers coating a nanoparticle surface can recognize
specific molecules just like an antibody.
MIT chemical engineers have developed a novel way to generate
nanoparticles that can recognize specific molecules, opening up a new
approach to building durable sensors for many different compounds, among
other applications.
To create these “synthetic antibodies,” the researchers used carbon
nanotubes — hollow, nanometer-thick cylinders made of carbon that
naturally fluoresce when exposed to laser light. In the past,
researchers have exploited this phenomenon to create sensors by coating
the nanotubes with molecules, such as natural antibodies, that bind to a
particular target. When the target is encountered, the carbon nanotube’s
fluorescence brightens or dims.
The MIT team found that they could create novel sensors by coating the
nanotubes with specifically designed amphiphilic polymers — polymers
that are drawn to both oil and water, like soap. This approach offers a
huge array of recognition sites specific to different targets, and could
be used to create sensors to monitor diseases such as cancer,
inflammation, or diabetes in living systems.
“This new technique gives us an unprecedented ability to recognize any
target molecule by screening nanotube-polymer complexes to create
synthetic analogs to antibody function,” says Michael Strano, the Carbon
P. Dubbs Professor of Chemical Engineering at MIT and senior author of
the study, which appears in the Nov. 24 online edition of
Nature
Nanotechnology.
Lead authors of the paper are recent PhD recipient Jingqing Zhang,
postdoc Markita Landry, and former postdocs Paul Barone and Jong-Ho Kim.
Synthetic antibodies
The new polymer-based sensors offer a synthetic design approach to the
production of molecular recognition sites — enabling, among other
applications, the detection of a potentially infinite library of
targets. Moreover, this approach can provide a more durable alternative
to coating sensors such as carbon nanotubes with actual antibodies,
which can break down inside living cells and tissues. Another family of
commonly used recognition molecules are DNA aptamers, which are short
pieces of DNA that interact with specific targets, depending on the
aptamer sequence. However, there are not aptamers specific to many of
molecules that one might want to detect, Strano says.
In the new paper, the researchers describe molecular recognition sites
that enable the creation of sensors specific to riboflavin, estradiol (a
form of estrogen), and L-thyroxine (a thyroid hormone), but they are now
working on sites for many other types of molecules, including
neurotransmitters, carbohydrates, and proteins.
Their approach takes advantage of a phenomenon that occurs when certain
types of polymers bind to a carbon nanotube. These polymers, known as
amphiphilic, have both hydrophobic and hydrophilic regions. These
polymers are designed and synthesized such that when the polymers are
exposed to carbon nanotubes, the hydrophobic regions latch onto the
tubes like anchors and the hydrophilic regions form a series of loops
extending away from the tubes.
These loops form a new layer surrounding the nanotube, known as a
corona. The MIT researchers found that the loops within the corona are
arranged very precisely along the tube, and the spacing between the
anchors determines which target molecule will be able to wedge into the
loops and alter the carbon nanotube’s fluorescence.
Molecular interactions
What is unique about this approach, the researchers say, is that the
molecular recognition could not be predicted by looking at the structure
of the target molecule and the polymer before it attaches to the
nanotube.
“The idea is that a chemist could not look at the polymer and understand
why this would recognize the target, because the polymer itself can’t
selectively recognize these molecules. It has to adsorb onto the
nanotube and then, by having certain sections of the polymer exposed, it
forms a binding site,” Strano says.
Laurent Cognet, a senior scientist at the Institute of Optics at the
University of Bordeaux, says this approach should prove useful for many
applications requiring reliable detection of specific molecules.
“This new concept, being based on the molecular recognition from the
adsorbed phase itself, does not require the use of antibodies or
equivalent molecules to achieve specific molecule recognitions and thus
provides a promising alternative route for ‘on demand’ molecular
sensing,” says Cognet, who was not part of the research team.
The researchers used an automated, robot-assisted trial and error
procedure to test about 30 polymer-coated nanotubes against three dozen
possible targets, yielding three hits. They are now working on a way to
predict such polymer-nanotube interactions based on the structure of the
corona layers, using data generated from a new type of microscope that
Landry built to image the interactions between the carbon nanotube
coronas and their targets.
“What’s happening to the polymer and the corona phase has been a bit of
a mystery, so this is a step forward in getting more data to address the
problem of how to design a target for a specific molecule,” Landry says.
The research was funded by the National Science Foundation and the Army
Research Office through MIT’s Institute for Soldier Nanotechnologies.
MIT; November 24, 2013