Synthetic biology, the manufacture of previously unseen biologics, proffers unlimited potential to manipulate or rebuild imperfect processes within the body on the nanoscale.  Mimicking biological processes by engineering nanostructures for single-cell transplants represents an elegant strategy for addressing problems in various scientific fields. Now, a study from researchers at the University of Basel successfully integrates artificial organelles into the cells of living zebrafish embryos. The team states their innovative approach using artificial organelles as synthetic cellular implants offer new potential in treating a range of diseases. The opensource study is published in the journal Nature Communications.

Previous studies have shown in the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. It is, therefore, highly desirable to produce made-to-order synthetic cellular transplants and introduce them into cells where their activity can be controlled in response to external factors.  These environmental factors could involve a change in pH values or reductive mechanisms, or carrying enzymes able to convert a pharmaceutical ingredient into the active substance under specific conditions. The current study combines biomolecules with artificial compartments, a biomimetic strategy to develop artificial organelles as cellular implants, with stimuli-triggered enzymatic activity in zebrafish embryos.

The current study develops artificial organelles in zebrafish embryos based on tiny capsules capable of forming spontaneously in solution from polymers, enclosing various macromolecules such as enzymes. Results show the artificial organelles contain a peroxidase enzyme triggered to act when specific molecules penetrate the wall of the capsules. Data findings show chemically modified natural membrane proteins integrated into the wall of the capsules act as gates that open or contract according to the glutathione concentration in the cell.

Results show at low glutathione values the pores of the membrane proteins are closed in zebrafish embryos, meaning no substances can pass. Data findings show if the glutathione concentration rises above a certain threshold, the protein gate opens and substances from outside can pass through the pore into the cavity of the capsule. The group states they are converted by the enzyme inside so the product of the reaction can leave the capsule through the open gate.

The team surmises they have succeeded in integrating artificial organelles into the cells of living zebrafish embryos. For the future, the researchers state the idea of using artificial organelles as cell implants with the potential to produce active pharmaceutical compounds opens up new perspectives for patient-oriented protein therapy.

Source: University of Basel

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