Scientists are one step closer to producing synthetic cells that can interact with living matter

For decades, researchers have been fascinated by the process of cell division, a highly intricate process driven by a precise cocktail of components. To better understand this phenomenon, researchers have been trying to create synthetic cells that mimic nature.

While it will take some time before we have fully functional synthetic cells, a study led by researchers from DWI—Leibniz Institute for Interactive Materials has brought this goal one step closer. The study describes the integration of cell division machinery in synthetic cells, a breakthrough in the field.

The research at DWI was directed by former working group leader César Rodriguez-Emmenegger, who is now a professor at IBEC Barcelona.

Replicating bacterial cell division

Creating synthetic cells that mimic biological functions and behavior is one of the greatest challenges in the field of bioinspired interactive materials. To create synthetic cells, researchers replicated cell membranes that can interact with the active cell division machinery (divisome) without losing their functionality.

A divisome is a highly complex protein system that is responsible for cell division in bacteria. It creates a ring around the middle of the bacterial cell, which then constricts and cuts the bacterial cell in two.

Divisome works by interacting with the synthetic cell membrane with the same strength and dynamic as with natural membranes, a challenge not accomplished before.

The divisome proteins won't attach if the membrane doesn't have the right thickness. Another is the charge, as the balance of attraction and repulsion between the proteins and the membrane is crucial. Finally, the membrane needs to be highly mobile, flexible, and stable so that it can withstand the forces exerted on it by the proteins.

To overcome these barriers, researchers designed new macromolecular building blocks and programmed them to assemble in the membrane and interact with the divisome in a predetermined manner. This approach allowed the research team to accurately reproduce the behavior of the divisome in synthetic cells.

Previously researchers have tried to mimic this process in a variety of systems, but they had only succeeded when the system was built from lipids – the natural components that make up cell membranes.

Together with Prof. Herrmann, Vice Scientific Director at DWI, Prof. Rodriguez-Emmenegger's team also showed the development of ionically linked comb polymers that self-assemble in water into vesicles with biomimetic membrane thickness. They named these ionic combisomes (i-combisomes).

They then created bacteria-combisome hybrids by capturing living bacterial cells and integrating their cell periphery into the synthetic membrane, a milestone never achieved before.

The high degree of resemblance in the i-combisomes, the tunability of the chemical and biological composition of the membrane, and the ability to fuse with living matter can potentially lead to synthetic cells with enhanced functions.

A new avenue to improve medicine

Synthetic cells can be programmed to perform functions that can't be performed by normal cells, opening up a host of possibilities in biomedicine. For instance, a synthetic cell could be designed to mimic an immune cell and fine-tuned to specifically act on cancer cells. This could lead to increased therapeutic efficacy and reduced risk of toxic side effects of drugs. An artificial cell could be used to sense changes in the body and respond by releasing compounds necessary for a healthy body, such as insulin.

The study was published in the journal Advanced Materials.

Abstract:

The integration of active cell machinery with synthetic building blocks is the bridge toward developing synthetic cells with biological functions and beyond. Self-replication is one of the most important tasks of living systems, and various complex machineries exist to execute it. In Escherichia coli, a contractile division ring is positioned to mid-cell by concentration oscillations of self-organizing proteins (MinCDE), where it severs membrane and cell wall. So far, the reconstitution of any cell division machinery has exclusively been tied to liposomes. Here, the reconstitution of a rudimentary bacterial divisome in fully synthetic bicomponent dendrimersomes is shown. By tuning the membrane composition, the interaction of biological machinery with synthetic membranes can be tailored to reproduce its dynamic behavior. This constitutes an important breakthrough in the assembly of synthetic cells with biological elements, as tuning of membrane–divisome interactions is the key to engineering emergent biological behavior from the bottom-up.