14 October 2022

Light and heat

Artificial cells turn heat into a chemical signal

Yulia Panchenko, PCR.news

Artificial cells are designed in such a way that they resemble biological cells in form, function and behavior. They are used as simplified models that help to understand the structure of cells, but in the future they can be used for biomedicine and biotechnology purposes. It is much easier to give artificial cells the necessary features than natural ones. On the other hand, we cannot yet repeat the entire metabolic, regulatory and behavioral complexity of biological cells. But you can try to combine these two elements into one system. The difficulty is that to do this, artificial and natural cells must "communicate". Attempts to solve this problem have already been made, but mainly using chemical signals. Researchers from Imperial College London have noticed physical stimuli.

The authors created two types of artificial cells based on vesicles — light-sensitive and temperature-sensitive. In the first case, vesicles were obtained using a lipid capable of photopolymerization. Under the influence of light, the lipid forms pores in the membrane of the artificial cell, releasing its contents outside. A lipid with a melting point of about 41.5°C was used to create a thermosensitive cell. With a little heating, the cell membrane becomes more permeable, and the contents come out. Previously, such systems have already been used to deliver drugs against cancer.

Isopropyl-β-d-1-thiogalactopyranoside (IPTG), a highly stable lactose analog, was chosen as signaling molecules for the light—activated system. It activates the lac operon of Escherichia coli, which in turn activates the production of yellow fluorescent protein (YFP). YFP is produced when IPTG exits the artificial cell. If the vesicles are not illuminated, then about 43% of the E cells. coli express YFP, after illumination this number doubles (85%). The artificial cells remained stable in the nutrient medium during incubation.

However, light penetrates poorly into tissues and weakens in liquids. From this point of view, heat is easier to use. So temperature-controlled artificial cells can find use if it is necessary to activate them in the depths of tissues.

Thermosensitive artificial cells contained rhamnose. When the temperature rises, rhamnose comes out and activates a promoter that controls the expression of green fluorescent protein in E cells. coli. Protein expression increased by 1.4 and 1.3 times when heated ex situ and in situ. The result can be improved by modifying the solution in which the cells are located.

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The authors also described how an artificial cell releases its cargo under the influence of a stimulus. So, they showed that the artificial cell is not destroyed at the same time. However, cells activated by light cannot be heated to physiological temperatures, because this also causes them to release cargo.

The authors say that they have created a universal platform where artificial cells act as a transmitter, converting physical stimuli into chemical ones, to which the cell can already respond. Potentially, the platform can also be used for incentives of a different nature. At the same time, the natural cell does not need to be genetically modified, since the elements responding to physical stimuli are placed in an artificial cell. The authors also believe that their platform will contribute to the creation of artificial organelles in the future.

Article by Gispert et al. Stimuli-responsive vesicles as distributed artificial organelles for bacterial activation is published in the journal PNAS.

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