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Posted: Mar 26, 2015

Smart materials become 'alive' with living bacteria in supramolecular assemblies

(Nanowerk Spotlight) Supramolecular chemistry deals with molecular building-blocks that interact with each other in a dynamic manner, similar to what is seen in nature. Taking advantage of this, several 'smart' materials have been developed for biomedical applications by careful design of these building-blocks. These materials have especially interesting properties like self-healing and responsiveness to light and electricity.
"So far these materials have mostly been developed using artificially synthesized molecules and some simple proteins, which effectively limits the properties that can be endowed upon such materials," Pascal Jonkheijm, a professor at the MESA+ Institute for Nanotechnology and the University of Twente, tells Nanowerk. "In our new work, we explored the possibility of developing a bacterial strain with the ability to interact dynamically with one such popular supramolecular building-block – a pumpkin-shaped hollow molecule named Cucurbit[8]uril (CB[8])."
By doing so, Jonkheijm, who heads research into Bioinspired Molecular Engineering, and his team, were able to show that living cells can also be used as a component in supramolecular smart materials. Their novel strategy introduces specific, dynamic and reversible supramolecular functionality on the bacterial cell surface by adopting a bacterial display system that has been used before exclusively to identify high affinity peptides for various proteins.
Although this study focused specifically on CB[8], the techniques demonstrated by the researchers can also be used to develop and study other strains for different host molecules.
"This could essentially allow us to give these material exciting new properties like motility, growth and resistance against external agents," says Jonkheijm
A paper on these results has been published in the March 4, 2015 online edition of ACS Nano ("Incorporating Bacteria as a Living Component in Supramolecular Self-Assembled Monolayers through Dynamic Nanoscale Interactions").
Development of a CB[8]-addressable bacterial strain
Development of a CB[8]-addressable bacterial strain. Min-23 construct 1 contains peptide sequence GGWGG in one loop. This was genetically fused to a modified outer membrane protein eCPX, which enabled it to be displayed on the outer membrane and bind CB[8].(Reprinted by permission from American Chemical Society) (click on image to enlarge)
While some advances have been made by other groups where supramolecular elements were introduced on cell membranes by merging artificially made membranes, this is the first time where the cells were made to produce and display supramolecular elements on their surfaces through genetic engineering.
"Since we have done this in bacterial cells, in principle, we can grow an infinite amount of cells with these supramolecular properties," Jonkheijm points out. "This laboratory bacterial strain was originally derived from the flora in human intestines, which means that our supramolecular strain could be incorporated in materials for biomedical applications."
Supramolecular materials have been designed with various different types of building-blocks and having many exciting properties. Jonkheijm's group has also been actively developing such dynamic and responsive materials to address biomolecules, cells and even tissues.
"The logical next step in the evolution of such materials was to incorporate living cells as active components," he notes. "However, this has proven to be extremely challenging and has been approached by only a few groups. We felt that the power of bacterial genetic engineering could help to address this challenge in a robust and sustainable manner and so we attempted this project."
This work currently addresses the issue of incorporating living cells in supramolecular materials only at a fundamental level. According to the researchers, one could imagine that these bacteria can carry within the bloodstream microscopic cargo, like drugs in a micro-capsule, and when triggered release this cargo at a particular site, like a cancerous or infected cell.
Living cells incorporated in supramolecular materials could possibly also be designed to secrete other components of the material, allowing them to heal the material or make it grow. Several such possibilities could be achieved to expand upon the impressive properties already available in supramolecular materials developed so far.
"The future of this research field is very bright and is limited only by our imagination and understanding," says Jonkheijm "These new discoveries and several others that are being made every day will allow us to make smart materials with properties that mimic and surpass those found in nature. Such materials can have an extremely wide range of applications from biosensors and implant coatings to even electronics."
He cautions, though, that there are several challenges facing them, largely regarding the understanding of these systems. Living systems are extremely difficult to predict and a massive amount of trials and tedious analysis is required to understand the various processes involved.
"Large strides cannot be hastily made and an immense amount of knowledge needs to be gathered and connected from various field," Jonkheijm concludes. "However, in the past few decades impressive advances in supramolecular materials have been made and with the same amount of effort, we will soon see several of these materials being incorporated in real world situations."
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