Polymersomes – an alternative skin for synthetic cells

European researchers have shown that cell-like structures made from polymers can host cellular processes and therefore offer an alternative to lipid-based membranes for the building of synthetic cells. These polymer-based containers could provide a new perspective for understanding the mechanism of life and are also of great interest for industrial applications.

Synthetic cell researchers aim to deepen our understanding of living systems by trying to reproduce cellular mechanisms outside of cells and ultimately in cell-like structures. While some researchers are using elements present in living cells, such as lipids, to build the outer layer of these cell-like structures, others are turning to polymers, mostly man-made components, to form polymer-based containers, i.e. polymersomes.

A “one-pot” method for making polymersomes and incorporating components without degrading them

In a new study published in December in Nature Chemistry, German, British and Swiss researchers have demonstrated the ability of polymersomes to encapsulate components that are important for cellular processes, without degrading them. In other words, polymersomes constitute a potential membrane for synthetic cells. But the idea of using polymers to build biomimetic membranes was not so simple, as Andrea Belluati, who co-led the study with Sètuhn Jimaja (University of Fribourg, Switzerland), explained.

“The conditions for chemically initiating the self-assembly of polymer chains damage the biological molecules. This is an obstacle for researchers who are trying to build synthetic cells in one pot, i.e. to mix from the start both the elements that form the polymer membrane and the biological components essential to the cellular processes that the membrane must encapsulate,” said the junior group leader for TU Darmstadt in Germany and member of the Bruns group.

To overcome this problem, Andrea and his colleagues employed a method for forming polymer chains that uses enzymes, catalysts present in cells, to initiate polymer synthesis. Simultaneously, they integrated this method with the concept of Polymerization-Induced Self-Assembly (PISA), a technique that forms vesicles concurrently with polymer synthesis. This technique closely mirrors the natural formation of cell membranes.

“By applying this enzymatic method, we were able to produce a high quantity of micro-metre-sized vesicles with high encapsulation efficiency. For example, we encapsulated actin, which remained active and formed a very unusual internal structure. We were also able to express several proteins inside these polymersomes, having successfully encapsulated plasmids and cell lysate.”

“We have therefore shown that we can replace cell membranes with artificial membranes, using biochemical rather than chemical reactions.”

The advantages of using polymer-based membranes

“One of the fundamental questions some researchers like myself are asking is whether or not life is defined by its chemical ingredients and whether we can reproduce life-like behaviour using other molecules.”

The use of alternative membranes for the construction of synthetic cells could therefore help to improve our understanding of life.  Polymersomes also tend to be more stable than their lipid-based counterparts. “They last longer, withstand harsh conditions better, are easier to work with and, in some cases, do not trigger immune system reactions. Their properties are therefore very interesting for industry, for example in biomedicine.”

He added: “We are no longer limited by lipids. We can now easily build structures similar to lipid-based membranes but with greater stability and in large quantities. We currently use conventional polymers, but some researchers are working on polymers with additional properties such as temperature-responsive polymers. So, with a polymer membrane, we could activate processes in cell-like containers using stimuli that do not affect living cells.”

Next steps: size and shape control, inner compartments and growth

Andrea and Nico Bruns’ group are continuing to develop polymersome methods for building synthetic cells, focusing on size and shape control and the creation of internal compartments through a second polymerisation cycle.

“We would also like, in the near future, to be able to use fully degradable polymers that remain robust and last longer than lipid-based containers,” concluded Andrea.

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Breakthrough in the synthesis of artificial cells – Press release

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