Biosensors play a crucial role in diagnostics and synthetic cell biology as they can detect target chemicals and biomolecules. However, existing biosensor designs have limitations in recognizing complex and flexible molecules. Professor Patrick Barth and his team at EPFL have developed a novel computational approach to overcome these challenges.
The researchers created a computer-based system, a computational framework, for designing protein complexes with dynamic shape and function. Unlike traditional static approaches, this framework allows for the exploration of previously unexplored protein sequences and enables the activation of protein groups in new ways, even different from their natural function.
Using this method, the team engineered synthetic receptors capable of sensing and responding to multiple natural or engineered molecular signals. These receptors interact with flexible ligands through allosteric triggers, similar to natural receptors. However, they improve and rewire the transmission of signals, enhancing signal transmission through optimized dynamic couplings.
The research demonstrates that combining a flexible sensing layer with a robust signal transmission layer is a characteristic feature of G protein-coupled receptors (GPCRs), which are crucial receptors in cells involved in various cellular processes.
The designed biosensors were successfully employed to drive cell migration in lymphocytes, enhancing their efficiency in responding to chemokines. This has implications for improving immune cell recruitment in diseases where the process is suboptimal, presenting potential therapeutic applications.
The ability to design synthetic receptors that can sense and respond to specific signals opens up possibilities in synthetic cell biology. It provides a powerful tool for precise control over cellular processes, with applications ranging from cancer treatment, where engineered cytotoxic lymphocytes with enhanced chemotaxis could target tumor sites more effectively, to various therapeutic contexts.