Goodbye, dark Satanic mills. Hello, glowing molecular factories. We’re looking at a new industrial revolution. Instead of cramming machines and workers into buildings, we’ll be stuffing artificial organelles into natural vesicles. And if anything glows, it won’t be an ember of coal or a piece of smelted metal. It’ll be a molecular indicator, a fluorescence protein, confirming that production is in full swing.
Molecular factories don’t have to be fully equipped artificial cells, which have shown promise as producers of therapeutics or staging areas for in vitro–specific reactions. No, molecular factories can be stripped-down versions of living cells, potentially expediting the development of in vivo applications. All a molecular factory needs from a donor cell is its natural cytoplasm and membrane. These provide the environment to which artificial elements may be introduced.
By avoiding the complexity of a fully equipped artificial cell, a stripped-down molecular factory may simplify inspection regimes, which need to confirm that productive elements work smoothly, avoiding breakdowns and toxic effects.
Pilot molecular factories have been built by scientists at the University of Basel. They supplemented giant plasma membrane vesicles derived from donor cells with nanometer‐sized artificial organelles. The scientists hoped to create molecular factories that would mimic the architecture and functionality of eukaryotic cells. To see if they succeeded, the scientists evaluated the performance of their molecular factories in vivo.
Detailed findings from this work appeared January 9 in Advanced Science, in an article titled, “Bioinspired Molecular Factories with Architecture and In Vivo Functionalities as Cell Mimics.”
“It is demonstrated that reactions inside artificial organelles take place in a close‐to‐nature environment due to the unprecedented level of complexity in the composition of the molecular factories,” the article’s authors wrote. “It is further demonstrated that in a zebrafish vertebrate animal model, these cell mimics show no apparent toxicity and retain their integrity and function.”
The molecular factories represent a group effort. First, researchers led by Cornelia Palivan, PhD, and Wolfgang Meier, PhD, both professors, department of chemistry, University of Basel, designed artificial organelles, that is, distinct compartments of cells. They loaded these soft, synthetic capsules with enzymes and equipped them with membrane proteins that act like “gates.” These gates allow molecules involved in the enzymatic reaction to enter and leave the capsule.
Subsequently, the natural cells were loaded with these artificial organelles. After stimulation, the cells produced natural micrometer-size vesicles. These possess a natural cell membrane and cytoplasm, enclose the artificial organelles, and can therefore function as a molecular factory.
The molecular factories were injected into zebrafish embryos by researchers from the group led by Jörg Huwyler, PhD, head of the division of pharmaceutical technology, department of pharmaceutical sciences, University of Basel. In this animal model, they produced the desired compound, which was catalyzed by the enzyme in the artificial organelle. The viability of the animal was not compromised by the injection.
“This combination of natural vesicles and small synthetic organelles is what makes the molecular factory,” explained Tomaz Einfalt, PhD, postdoctoral researcher and Martina Garni, PhD, postdoctoral researcher and both first authors of the paper. “Reactions that take place inside produce an end product, as also happens inside cells.”
Within the molecular factories, multiple components can be made and assembled into the end product. The biosynthetic vesicles can also transfer components from one cell to the other. Different molecular factories can be combined so that complex structures with high functionality can be created—the first step toward producing artificial cells in the laboratory or in living organisms.
The article’s authors asserted that their molecular factories possessed several advantages: highly varied composition, multicompartmentalized architecture, and preserved functionality in vivo. Consequently, the authors concluded that their molecular factories “open new biological avenues ranging from the study of biorelevant processes in robust cell‐like environments to the production of specific bioactive compounds.”