Advances in artificial cell architecture and complex function may make it possible to develop a way for pathologists to deliver biomarkers into living cells to diagnosis diseases and monitor patient response to therapies

For the first time, researchers have used polymers to produce an artificial eukaryotic cell with working organelles. Like a living cell, it successfully performed multiple chemical reactions. The importance for pathologists and clinical laboratory professionals is that the same technology could allow scientists to develop different ways to deliver biomarkers into cells to reveal diagnostic information—and perhaps even track a patient’s progress in therapy.

Dutch Researchers Get Closer to Unlocking the Complexity of a Living Cell

Biomarkers are increasingly important in the clinical management of complex diseases. Nevertheless, the ability to discover new ones has remained constrained by dependence on endogenous biomolecules.

Now, researchers Jan van Hest, Ph.D., and Ph.D. candidate Ruud Peters of Radboud University Nijmegen in The Netherlands have developed an artificial eukaryotic cell. They used polymers to form both the cell wall and the functioning organelles within a “polymersome-in-polymersome” architecture. Polymersomes are a class of artificial vesicles used to enclose a solution, according to Wikipedia.

It was a major accomplishment for researchers at Radboud University Nijmegen in The Netherlands to create an artificial eukaryotic cell with working organelles that function like a living cell. Jan van Hest, Ph.D. (pictured above), led the research team. Experts believe this will be a method that can be used to insert biomarkers into living cells to deliver diagnostic data. If this comes about, it would give pathologists and clinical laboratory scientists a new way to conduct medical laboratory testing. (Photo copyright Radboud University Nijmegen.)

It was a major accomplishment for researchers at Radboud University Nijmegen in The Netherlands to create an artificial eukaryotic cell with working organelles that function like a living cell. Jan van Hest, Ph.D. (pictured above), led the research team. Experts believe this will be a method that can be used to insert biomarkers into living cells to deliver diagnostic data. If this comes about, it would give pathologists and clinical laboratory scientists a new way to conduct medical laboratory testing. (Photo copyright Radboud University Nijmegen.)

 

“[We formed] a multi-compartmentalized structure, which shows structural resemblance to the cell and its organelles,” van Hest and Peters wrote in a study published in the first 2014 issue of the journal Angewandte Chemie. Nature Chemistry also highlighted the study.

Strategies to Control Biological Processes within a Living Cell

It is challenging for chemists to match the chemistry in living cells, according to a story published by zeitnews.org. In a living cell, simultaneous complex reactions are taking place in various separate compartments in a very small area with incredible efficiency. Chemists attempt to imitate the cell in various ways to better understand the structural and functional complexity.

Previous microencapsulated reactors have not possessed the complexity required to mimic cellular reaction pathways that take place in multiple successive compartments, the researchers noted in the study. Better understanding of this compartmentalization has been a key goal of scientists seeking to break through the complexity of a natural cell.

“Nature employs several approaches to ensure the integrity of the—mostly enzyme-catalyzed—synthetic pathways within a cell,” explained van Hest in a story published by Nanowerk. “[O]ne of the most important [of these is] compartmentalization. This approach, which isolates the catalytic cycle, prevents interference by other compounds, and enables regulation of the flux of molecules in and out of the microenvironment.”

In other words, the polymeric membranes of the artificial organelles allow substrates and reaction products to freely diffuse in and out of the tiny vesicular nanoreactors. At the same time, the enzymes remain trapped inside the reactor polymersomes because of their large size, explained Peters in an article published on the university’s website. This mimics naturally occurring microcapsules, he observed.

Polymersomes as Artificial Organelles

To construct the organelles, van Hest and Peters built tiny semi-porous polymersomes filled with enzymes. They then placed these enzyme-filled nanoreactors inside a water droplet. Next, they covered the water droplet with a polymer layer to create the cell wall.

The researchers succeeded in setting off a cascade of chemical reactions within theartificial organelle. By incorporating several enzymes into a polymeric capsule, they enabled the implementation of reaction cascades inside the cell, according to the university’s website.

The team used fluorescence to show that the planned cascade of chemical reactions did in fact occur. “Just like in the cells in our bodies, the chemicals [were] able to enter the cell plasma, following the reaction in the organelles, to be processed elsewhere in the cell,” explained Peters in a university press release.

The study thus demonstrated structural and functional control in a multi-compartmentalized system.

Functioning Artificial Eukaryotic Cell

The approach moves science one step closer to artificial cell-like devices. Of greater interest to pathologists and clinical laboratory professionals is the more immediate potential for screening and diagnosis of disease. “[T]hese nanoreactors can… be very useful for diagnostics and therapeutics, due to their protective shell,” observed van Hest in the Nanowerk piece.

For The Dark Report and Dark Daily readers, a question might be:  Might there be a role for pathologists, Ph.D.s, and laboratory scientists in advancing personalized medicine by fabricating customized biomarkers with this artificial cell technology, thus supporting care from the medical laboratory with technology used in a way that is different from today’s use of IVD test kits?

—Pamela Scherer McLeod

Related Information:

First plastic cell with working organelle

Artificial organelles and cell mimics

World-first eukaryotic cell made from plastic

Cascade Reactions in Multicompartmentalized Polymersomes

Nano-enabled synthetic biology

Another nanotechnology example of mimicking nature: nanoreactors for one-pot multistep reactions

First plastic cell with working organelle

Synthetic cells (PDF)

;