Crosstalk Between Living Cells and Synthetic Nanoassemblies Feedback-Controlled Peptide Assemblies Enable Adaptive Communication with Living Cells
A groundbreaking study reveals how synthetic nanostructures can be dynamically regulated within living cells to prevent toxic accumulation and restore physiological homeostasis. Researchers from the Max Planck Institute for Polymer Research in Mainz and the University of Münster established a closed-loop system that couples supramolecular peptide transformations with bacterial genetic circuits. By establishing programmable influx–efflux cycles, the system actively clears internalized nanoparticles and re-establishes redox and energy homeostasis, overcoming a longstanding bottleneck in nanomedicine.
Using a light-responsive photosensitizer–peptide conjugate, the team designed a reversible redox switch between methionine and methionine sulfoxide that drives morphological transitions between nanofibers and nanoparticles. Upon visible-light irradiation, oxidized nanoparticles are internalized into engineered bacteria. To counteract the perturbations caused by internalized NPs, engineered bacteria activate the expression of MetO reductases in response to photo-oxidative stress. The internalized NPs are intracellularly enzymatically reduced such that they are expelled as reduced NFs, setting the stage for subsequent cycles. The concept presented here paves the way for the interlinked network between dynamic supramolecular assemblies and cellular regulatory behaviors.
The work, published in Nature Chemical Biology, highlights a new paradigm for engineering adaptive biomaterials that operate in harmony with biological systems. By integrating supramolecular chemistry and synthetic biology, the work demonstrates how synthetic materials can transition from passive intracellular accumulators to feedback-responsive, homeostasis-preserving systems. This strategy opens new opportunities for responsive nanomedicine, programmable cell-based therapeutics, engineered living materials, and next-generation regenerative nanotherapies.
