Cheemeng Tan, Department of Biomedical Engineering, UC Davis
Engineering programmable, dynamic materials using bio-inspired mechanisms
Dynamic, bio-mimetic materials operate autonomously by sensing and adapting to their surrounding environment. Engineered to respond to a multitude of extracellular signals (e.g., proteases, pH, light), these materials generally react by releasing small molecules into their surroundings. While these state-of-the-art engineered materials can sense their environment, two-way communications, like those prevalent in natural systems, remain difficult due to the myriad of interactions inherent in cell-like environments. Here, we exploit synthetic biology approaches to develop the first modular dynamic material that can perform two-way communications with natural cells. The dynamic material, also called artificial cell, mimics several key properties of natural cells, including synthetic membranes, molecular transport, gene expression, and cell-cell communication. They are assembled from the bottom up using lipids, DNA, protein synthesis machineries, NTP, amino acids, and various accessory proteins and chemicals. We demonstrate cell-cell communication under three scenarios: artificial cells signaling bacteria, bacteria signaling artificial cells, and artificial cells signaling each other. To guide the control of the systems, mathematical models are developed to describe the genetic circuitry of each system as well as the spatial distribution of the transmitters, receivers, and the diffusing signal molecules. Based on the basic modules, we further implement artificial cells that synthesize an antimicrobial peptide upon detecting the presence of bacteria. The antimicrobial peptide inhibits bacterial growth, providing an alternative strategy for the treatment of antibiotic-resistant bacteria. The development of communication between artificial cells and living cells provides further insight into cell-cell communication in general, opens the door for new therapeutic uses of artificial cells, and expands the capacity of artificial systems to mimic living ones.
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