A research group at the University of Basel has achieved a milestone by creating simple, environmentally-responsive cells equipped with artificial organelles. For the first time, they have also replicated natural intercellular communication in these proto-cells, taking inspiration from the way photoreceptors function in the eye. This advancement opens up significant avenues for fundamental research and medical applications.
Communication is vital for life—whether among bacteria or complex multicellular organisms, living entities depend on their cells’ capabilities to transmit, receive, and process signals. A team of researchers led by Professor Cornelia Palivan from the University of Basel, in collaboration with Nobel Prize winner Professor Ben Feringa from the University of Groningen, has successfully imitated this natural cell communication using synthetic cells, as reported in the scientific journal Advanced Materials.
Palivan and her team focus on tiny polymeric containers that can be filled with specific molecules and opened in a directed manner. In their latest project, they have taken it a step further: “We created micro-sized containers that mirror cells and are filled with specialized nanocontainers,” says Palivan. This technique enables them to construct simplified synthetic cells, also referred to as protocells, with organelle-like features.
The researchers introduce a system of protocells formed from polymers, biomolecules, and various nanocomponents that mimic signal relay in the eye’s retina. This system includes light-sensitive protocells acting as “senders” and other protocells serving as receivers.
Light activation
In the sender protocells, there are nanocontainers—effectively artificial organelles—whose membranes are embedded with unique light-responsive molecules called molecular motors. This design empowers the researchers to initiate communication between the two cells using a light pulse: when the sender cell is illuminated, the light-sensitive molecules trigger the nanocontainers to open, releasing their contents—referred to as substance A—into the interior of the sender cell.
Substance A can exit the sender cell through openings in its polymer shell, moving into the fluid surrounding the protocells until it enters the receiver cell through its own pores. Once inside the receiver cell, substance A interacts with synthetic organelles containing an enzyme that transforms it into a fluorescent signal. This fluorescence indicates successful signal transmission from the sender to the receiver.
Calcium ions to regulate the fluorescence signal
In the natural photoreceptors of the retina, calcium ions play a crucial role by moderating signal transmission to subsequent cells, helping the eye adjust to bright light. Similarly, the researchers designed the artificial organelles in the receiver cells to respond to calcium ions, allowing them to dampen the conversion of substance A into fluorescence.
A foundation for synthetic tissue
“By employing an external light pulse, we successfully triggered an organelle-driven signaling cascade and modulated it with calcium ions. Establishing a temporally and spatially controllable system inspired by natural cell communication is a groundbreaking accomplishment,” states Palivan.
This innovative development lays the groundwork for synthetically mimicking intricate communication networks found in living cells, enhancing our understanding of these systems. It also opens up possibilities for creating interactive networks between synthetic and biological cells, potentially leading to therapeutic innovations aimed at disease treatment or the development of synthetic tissue.