Washington: Researchers have developed a novel method for creating self-assembled protein/polymer nanostructures that are reminiscent of fibres found in living cells.
The work by Carnegie Mellon University offers a promising new way to fabricate materials for drug delivery and tissue engineering applications.
"We have demonstrated that, by adding flexible linkers to protein molecules, we can form completely new types of aggregates," said Tomasz Kowalewski, professor of chemistry in Carnegie Mellon`s Mellon College of Science.
"These aggregates can act as a structural material to which you can attach different payloads, such as drugs. In nature, this protein isn`t close to being a structural material," Kowalewski said.
The building blocks of the fibres are a few modified green fluorescent protein (GFP) molecules linked together using a process called click chemistry.
An ordinary GFP molecule does not normally bind with other GFP molecules to form fibres.
But when Carnegie Mellon graduate student Saadyah Averick, working under the guidance of Krzysztof Matyjaszewski, the JC Warner Professor of Natural Sciences and University Professor of Chemistry in CMU`s Mellon College of Science, modified the GFP molecules and attached PEO-dialkyne linkers to them, the GFP molecules appeared to self-assemble into long fibres.
Importantly, the fibres disassembled after being exposed to sound waves, and then reassembled within a few days.
Systems that exhibit this type of reversible fibrous self-assembly have been long sought by scientists for use in applications such as tissue engineering, drug delivery, nanoreactors and imaging.
The research team observed the fibres using confocal light microscopy, confirmed their assembly using dynamic light scattering and studied their morphology using atomic force microscopy (AFM).
They also observed that the fibres were fluorescent, indicating that the GFP molecules retained their 3-D structure while linked together.
To determine what processes were driving the self-assembly, Matyjaszewski and Kowalewski turned to Anna Balazs, Distinguished Professor of Chemical Engineering and the Robert v d Luft Professor at the University of Pittsburgh.
Balazs ran a computer simulation of the GFP molecules` self-assembly process using a technique called dissipative particle dynamics, a type of coarse-grained molecular dynamics method.
The simulation confirmed the modified GFP`s tendency to form fibres and showed that the self-assembly process was driven by the interaction of hydrophobic patches on the surfaces of individual GFP molecules.
In addition, Balazs`s simulated fibres closely corresponded with what Kowalewski observed using AFM imaging.
The findings are published in the Angewandte Chemie International Edition.