Researchers at New York University and the University of Chicago have developed artificial, fully synthetic cell-like structures that autonomously ingest, process, and push out material, recreating an essential function of living cells. Tests showed that when deployed in mixtures of different particles, the cell mimics—which are generated using only minimal inorganic materials—can carry out tasks that cells might carry out by active transport, including capturing, concentrating, storing, and delivering microscopic cargo. The team suggests that the new technology represents a blueprint for creating cell mimics that could have potential applications ranging from drug delivery to environmental science.

“Our design concept enables these artificial cell mimics to operate autonomously and perform active transport tasks that have so far been confined to the realm of living cells,” said Stefano Sacanna, PhD, associate professor of chemistry at NYU and lead author of the team’s published paper in Nature. “At the heart of the cell-like structure’s design is the synergy between an active element that powers it from the inside and the physical constraints imposed by the cell walls, allowing them to ingest, process, and expel foreign bodies.” Sacanna and colleagues describe the technology in a paper titled “Transmembrane transport in inorganic colloidal cell-mimics.”

A fundamental function of living cells is their ability to harvest energy from the environment and use it to actively pump molecules in and out of their systems, the authors explained. When energy is used to move these molecules from areas of lower concentration to areas of higher concentration, the process is called active transport. Active transport enables cells to take in necessary molecules like glucose or amino acids, store energy, and extract waste. “Active transport allows cells to reside in a constant state of non-equilibrium,” the team stated. “This condition powers advanced functionalities such as motility, sensing and autonomous self-replication.”

For decades, researchers have been working to create artificial cells—engineered microscopic structures that emulate the features and behavior of biological cells. But these cell mimics tend to lack the ability to perform complex cellular processes like active transport. “Unlike living cells, abiotic systems do not have the delicate biochemical machinery that can be specifically activated to precisely control biological matter,” the team continued.

To design their cell mimics, the researchers created a spherical membrane the size of a red blood cell using a polymer, as a stand-in for the cell membrane that controls what goes in and out of a living cell. They pierced a microscopic hole into the spherical membrane creating a nano-channel through which matter can be exchanged, imitating a cell’s protein channel. “Borrowing no materials from biology, our design uses hollow colloids serving as spherical cell-membrane mimics, with a well-defined single micropore,” they explained.

In order to perform the tasks required for active transport, the cell mimics needed a mechanism to power the cell-like structure to pull in and expel material. In a living cell, mitochondria and ATP provide the necessary energy for active transport. In the cell mimic, the researchers added a chemically reactive component inside the nano-channel that, when activated by light, acts as a pump. When light hits the pump, it triggers a chemical reaction, turning the pump into a tiny vacuum and pulling cargo into the membrane. When the pump is switched off, the cargo is trapped and processed inside the cell mimic. And when the chemical reaction is reversed, the cargo is pushed out on demand. “The anatomy of our cell-mimics comprises three key components: a semipermeable membrane, the result of a spontaneous ‘self-inflation’ process; a well-defined micropore for matter exchange; and an internal phoretic pump activated by light,” the team wrote. ‘At the heart of the cell’s design is the synergy between an active element that powers the cell from the inside and well-defined physical constraints imposed by the cell walls, allowing cell-mimics to ingest, process and expel foreign bodies.”

Source: Sacanna Lab/NYU

The internal phoretic pump, consisting of a solid photocatalyst trapped inside the cell’s body, effectively harvests and uses chemical energy from the environment to actively move cargo across the micropore. “The phoretic pump operates under blue light and in the presence of a low background concentration of hydrogen peroxide, which serves as fuel.” So when the cell-mimic is illuminated, fuel decomposition by the photocatalyst causes by-products to build up inside the cell, and this then sets a chemical concentration gradient across the membrane’s micropore. “Particles near the micropore are driven inside the capsule by a net phoretic force that results from the particle–gradient interaction,” thereby allowing the capsule to capture microscopic payloads.”

The design then allows for on-demand delivery of the contents, the researchers stated. “When loaded, cells can be stored for several months without any detectable cargo loss. The payload can be forced through the entropic barrier and ejected by reversing the sign of the phoretic interaction.”

The researchers tested the cell mimics in different environments. In one experiment, they suspended the cell mimics in water, activated them with light, and observed them ingesting particles or impurities from the water surrounding them, illustrating a potential application for cleaning microscopic pollutants out of water. “Think of the cell mimics like the PAC-MAN video game—they go around eating the pollutants and removing them from the environment,” said Sacanna.

In another experiment, they demonstrated that the cell mimics can swallow E. coli bacteria and trap them inside the membrane, potentially offering a new method for fighting bacteria in the body. “The active transport mechanism efficiently captures solid particulates, emulsion droplets and bacteria from various colloidal suspensions,” the scientists added. Another future application for the cell mimics could be drug delivery, given that they can release a preloaded substance when activated.

Source: Sacanna Lab/NYU

The researchers are continuing to develop and study cell mimics, including constructing variations that perform different tasks, and learning how different types communicate with each other. They suggest that their initial groundwork offers “… general and scalable design principles for fabricating minimal-ingredient abiotic cells, that can effect non-equilibrium transmembrane mass transport, like living cells.”

Previous articleCustomizing Cancer Therapy for STING Protein Activation
Next articleMicrobiome’s Metabolism Altered by Bioaccumulation of Medications