By varying the identity and spacing of the tethered molecules, researchers can make the technique applicable to a wide range of bait molecules including drugs, chemical warfare agents, and environmental pollutants. Ultimately, the researchers also hope to identify synthetic biomolecules that recognize neurotransmitters so that they can fabricate extremely small biosensors to study neurotransmission in the living brain.
In the brain, dozens of different small signaling molecules interact with thousands of large receptive proteins as part of the fundamental communication process between nerve cells. This cacophony of specific interactions is highly dependent on nanoscale molecular structure. One key to advancing our understanding of how the brain works is to identify the nature of the association between neurotransmitters and their binding partners. The technique of producing these high-affinity materials will be published in January 2008 in the journal Advanced Materials by a research team headed by Anne Milasincic Andrews, associate professor of veterinary and biomedical sciences, and including Paul S. Weiss, distinguished professor of chemistry and physics.
The process starts with a self-assembled monolayer (SAM), a single-molecule-thick layer that organizes itself on a surface. The molecules that make up the SAM terminate in and expose oligoethyleneglycol units that are known to prevent adhesion of proteins and other large biomolecules. Next, tether molecules are inserted into the defects that naturally occur in the SAM. Finally, a small molecule, in this case the neurotransmitter serotonin, is chemically linked to the tether molecules. Since the defects in the SAM occur at irregular but controllable intervals, serotonin molecules are prevented from clumping together. This is key to their being recognized by the correct proteins.
When the surface is exposed to a solution containing many different proteins, only those with high affinities for the tethered small molecule selectively attach to the surface. The bound protein molecules can then be identified in place or removed for characterization. "The tethered neurotransmitter acts like a fishing pole," says Andrews. "When the small molecule 'bait' is correctly placed on the surface, it captures much larger molecules that interact with it in a biologically specific way."
As a result of this inherent selectivity, it is possible to identify biomolecules, by function, from a sea of thousands of different types of molecules. Weiss adds, "The key to obtaining a highly specific association is producing optimal spacing of the tethered neurotransmitters. The ideal spacing allows large molecules to recognize the functional groups of the small molecule while avoiding nonspecific binding to the surface itself."
Because of their selectivity, these materials are suitable for a variety of investigations in biological systems. "Each neurotransmitter can bind to a number of different receptors in the brain," says Andrews. "Some of these receptors are known, but there are many more to identify. Also, the numbers of receptors are altered in different disease states and in response to treatment, and these capture surfaces could be used to study how groups of functionally related proteins change in a coordinated fashion."
The research team includes Mitchell Shuster, graduate student in physics, Amit Vaish, graduate student in bioengineering, Matthew Szapacs, then a graduate student in chemistry and now a research scientist at GlaxoSmithKline, and Beth Anderson, then a graduate student in chemistry and now a postdoctoral fellow. The work is a part of and supported by the Center for Nanoscale Science at Penn State, a National Science Foundation Materials Research Science and Engineering Center.
Barbara K. Kennedy | EurekAlert!
Brought to light – chromobodies reveal changes in endogenous protein concentration in living cells
21.09.2018 | NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen
A one-way street for salt
21.09.2018 | Julius-Maximilians-Universität Würzburg
The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.
This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.
Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...
Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.
"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...
A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.
Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...
Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.
An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...
21.09.2018 | Event News
03.09.2018 | Event News
27.08.2018 | Event News
21.09.2018 | Physics and Astronomy
21.09.2018 | Life Sciences
21.09.2018 | Event News