DNA-based receptors to help synthetic cells interact with their environment
Smell, taste, touch, sight, hearing: the human senses help us understand our surroundings and guide some of our decisions. Living cells may not have eyes or ears, but thanks to receptors on their membranes and a cellular process called cell signalling, they can collect information about their environment and respond to it when necessary and in a timely manner. Researchers at the University of Cambridge in the UK have recently developed synthetic membrane receptors from DNA to mimic the early stages of this process. They hope that their work on synthetic cell signalling will provide a useful tool for designing advanced bio-inspired systems and monitoring living cells.
How do the cells in our bodies know when to perform a task, such as starting or stopping the production of a protein, dividing to produce replicas of themselves, and moving? Like us, on a different scale, they study their environment. They collect information, communicate with other cells, or detect what is happening in their immediate environment through a process called cell signalling, which allows them to react quickly to any changes in the situation they detect.
What happens in the early stages of cell signalling: the role of cations
Cations are present everywhere, in the cytoplasm of cells and in the extracellular fluids surrounding cells, and serve many cellular functions, including cell signalling.
“Cells have receptors on their membranes that are sensitive to the presence of cations, molecules that carry a positive charge. Cations that are important for living organisms include calcium, magnesium, potassium and sodium,” said Roger Rubio-Sánchez, a researcher at the University of Cambridge.
“When cations are shuttled across membranes,” continued Roger, “cells interpret their presence or absence and trigger specific responses. During this process, regions of the membranes called ‘signalling hubs’ become the site of a chemical reaction that triggers a cascade of downstream responses in the cell, signalling that it needs to change something.”
Mimicking cell signalling: three important characteristics to replicate
Roger and Lorenzo Di Michele‘s team at the University of Cambridge, sought to design cell-like systems with three characteristics important for cell signalling: they possess receptors that are responsive to cations, these receptors can catalyse reactions in the presence of cations, and these systems can localise this catalytic activity in specific regions of the membrane, thereby imitating the emergence of signalling hubs.
DNA molecules to build cation-sensitive receptors
First, the researchers built DNA units and attached them to the membrane of vesicles. In the presence of cations, these DNA nanostructures have the property of assembling into G-quadruplexes.
“These G-quadruplexes are structures that exist in biology. Composed of DNA or RNA, they play a role in biological processes like the regulation of gene expression. We have used them to build the reactive units of the receptors,” explained Roger.
Localised catalytic activity
Thanks to the properties of G-quadruplexes, they demonstrated that their systems could accommodate a chemical reaction, in this case, the production of a fluorescent molecule, and that they could modulate the reaction speed by changing the cations present in the surrounding solution.
Finally, they localised this chemical reaction using membranes that possess specific regions called membrane domains. These domains display variations in the structural organisation of their lipid components. In this study, they formed membranes comprising two domains, a ‘disordered’ and an ‘ordered domain’, the latter describing a region where lipids are more densely packed.
“We used anchors that slightly prefer the ordered domain to attach the components that form the G-quadruplexes and thus the receptors to the membrane. When the receptors formed in the presence of cations, they had eight anchors and were therefore present almost exclusively in the ordered domain, which allowed us to localise their catalytic activity.”
A toolkit for synthetic cell engineering and cell monitoring
Researchers are continuing their efforts to build synthetic cells capable of interacting with their environment.
“We believe these receptors are a useful tool for those working on the design of bio-inspired systems,” Roger stressed. “We are currently looking to couple these receptors with other downstream responses, like protein production, but the structure-function relationship we have highlighted in our study can be used for other purposes.”
“I also think they are not exclusively reserved for the assembly of synthetic cells. For example, they could help monitor the activity of living cells and the cations around them.”
Original publication
Cation-Controlled Assembly, Activity, and Organization of Biomimetic DNA Receptors in Synthetic Cell Membranes
Elita Peters, Diana A. Tanase, Lorenzo Di Michele, and Roger Rubio-Sánchez
Journal of the American Chemical Society 2025
