Tiny implants for single-cells are functional in vivo.

Mimicking biological processes by engineering biomimetic 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 state that their innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases.  The opensource study is published in the journal Nature Communications.

Previous studies show that in the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. It is highly desirable to produce cellular transplants of this kind in the laboratory to introduce them into cells, and to control their activity in response to the presence of external factors, for example a change in pH values or reductive conditions, or carry enzymes able to convert a pharmaceutical ingredient into the active substance and release it 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 which are based on tiny capsules that form spontaneously in solution from polymers and can enclose various macromolecules such as enzymes. Results show that the artificial organelles contain a peroxidase enzyme that only begins to act when specific molecules penetrate the wall of the capsules and support the enzymatic reaction.  Data findings show that chemically modified natural membrane proteins integrated into the wall of the capsules, to control the passage of substances, act as gates that open according to the glutathione concentration in the cell.

Results show in zebrafish embryos that at a low glutathione value, the pores of the membrane proteins are closed, meaning that no substances can pass. Data findings show that 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 state that there, they are converted by the enzyme inside and the product of the reaction can leave the capsule through the open gate.

The team surmise they have succeeded in integrating artificial organelles into the cells of living zebrafish embryos.  For the future, the researchers state that 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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