Scientists overcome the membrane barrier with new cell receptors for synthetic cells

A Danish team led by Alexander Zelikin has succeeded in creating signalling receptors from scratch that allow the transfer of information across the sealed cell membrane of synthetic cells. Their results were published in March 2023 in Nature Communications.

Schematic and chemical illustration of the proposed concept of transmembrane signalling using synthetic receptors

Living cells are able to communicate with each other, to detect and adapt to changes in their environment. The mechanisms that allow this transfer of information across their sealed membrane are complex and rely mainly on transmembrane proteins, called signalling receptors. When an external molecule binds to these receptors, it does not enter the cell itself, but the external binding triggers a response inside the cells.

The Engineering of synthetic cells that are responsive to stimuli is a challenge and, until now, has mostly been accomplished by diffusion of signalling molecules through the membrane. Zelikin and his team sought to mimic nature and were able to achieve transmembrane signalling in synthetic cells using artificial receptors based on the tools of organic chemistry.

The design of synthetic receptors that mimic the mechanisms of those in living cells could have many applications, especially to enable communication between and with synthetic cells, and could potentially be used in the future in biosensing technologies.

Receptors designed with the tools of organic chemistry

Ane Bretschneider Søgaard, PhD student in Zelikin’s team and first author of the paper, explained:  “We wanted to create receptors that were strongly inspired by nature, but really simplified and that were not proteins* but small simple organic molecules.”

“We have designed signalling receptors that allow the transfer of information across a sealed membrane. Unlike natural receptors, they are small and triggered by enzymes. This makes them very interesting for sensing applications,” she added.

After this successful experiment, the team is now working on new variants of these receptors, with the ability to detect other enzymes or trigger other reactions inside the synthetic cells.

Read more about the synthetic receptors of Zelikin’s team:

Søgaard, A.B., Pedersen, A.B., Løvschall, K.B. et al. Transmembrane signaling by a synthetic receptor in artificial cells. Nat Commun 14, 1646 (2023).

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* Proteins are very large molecules composed of many smaller organic units, called amino acids