Fig. 7. (a and b) Working principle of protocell with built-in AIRS. (a) Mechanism of AIRS as a DNA computational core built inside the protocell. Step 1: recognition and tolerance. Pathogen DNA is recognized by AIRS and if the amount of pathogen DNA is below the threshold of immune tolerance, further immune response will not be triggered. Step 2: immune response. If the amount of pathogen is excessive, an RCA-based immune response will be accelerated and antibody-mimicry (RCA product) will be generated. Step 3: killing and memory. Pathogen DNA is specifically captured by generated antibody-mimicry via hybridization and subsequently digested by a restriction enzyme. (b) Pathogen DNA is injected from an artificial pathogen into a protocell via a mimicked infection process. The delivered pathogen DNA triggers AIRS inside the protocell and a mimicked host immune response is activated to eliminate the infected pathogen DNA via a DNA reaction network-based computation. Reproduced from ref. 95 with permission. Copyright 2018 American Chemical Society. (c–f) Design of biomolecular implementation of protocellular communication (BIO-PC). (c) Basic principle of a BIO-PC platform that can sense, process and secrete short ssDNA-based signals. The semipermeable membrane allows an input strand to diffuse into a protocell followed by activation of a DNA gate complex via toehold-mediated strand displacement reaction. (d) Individual protocells can be designed as functional modules and combined to implement more complex population behaviors such as detection, transduction, cascading, amplification, logic operation, and feedback circuit. (e) Protocells can be captured and imaged on a microfluidic protocell trap array. Right panel: confocal imaging of eight protocells showing time-dependent signal increase after activation. Scale bar, 50 μm. Reproduced from ref. 97 with permission. Copyright 2019 Springer Nature.