Network topology–directed design of molecular CPU for cell-like dynamic information processing

Abstract

Natural cells (NCs) can automatically and continuously respond to fluctuant external information and distinguish meaningful stimuli from weak noise depending on their powerful genetic and protein networks. We herein report a network topology–directed design of dynamic molecular processing system (DMPS) as a molecular central processing unit that powers an artificial cell (AC) able to process fluctuant information in its immediate environment similar to NCs. By constructing a mixed cell community, ACs and NCs have synchronous response to fluctuant extracellular stimuli under physiological condition and in a blood vessel–mimic circulation system. We also show that fluctuant bioinformation released by NCs can be received and processed by ACs. The molecular design of DMPS-powered AC is expected to allow a profound understanding of biological systems, advance the construction of intelligent molecular systems, and promote more elegant bioengineering applications.

A Dynamic Control Center Based on a DNA Reaction Network for Programmable Building of DNA Nanostructures

“…The time-dependent concentration changes of species in the feed-forward pathway were used to fit rate constants, as given in Table S7 and S8. By using this set of rate constants, the time-dependent concentration changes of species were computationally simulated (Supplementary Note S1), , which corresponded to the experimental data. These results were also supported by electrophoresis analysis, which showed the almost entire conversion of ABC to CD with an input signal and only negligible leaks without an input signal after 2 h of reaction time (Figure C).…”

“…As a further exploration of the bionic application of our system, we built the DFFCS-controlled DNA nanotube inside water-in-oil droplet-based protocells as an artificial cytoskeleton to mimic the dynamic behavior of microtubules in natural cells. We used water-in-oil droplets (Figure S27) instead of giant unilamellar vesicles (GUV) , because surfactant stabilized droplets remained stable as an isolated environment without coalescence for several days, while GUVs ruptured in only a few hours after encapsulating the DFFCS-controlled DNA nanotube system (Figure S28). To trigger the DFFCS-controlled DNA nanotube system inside protocells, we blocked the initiator I by using a complementary strand with two inserted light responsive PC-linkers (Figure A).…”

“…The procedures to synthesize GUVs were based on the inverted microemulsion method of water in oil with some modifications. , Briefly, 10 μL of 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphocholine (POPC) (50 mg/mL) dissolved in 1.5 mL chloroform was first completely dried. Then, 1.5 mL of mineral oil was added to dissolve the lipid film by incubating at 85 °C about 1 h. Meanwhile, DNA reaction network modulars were mixed in 1× PBS buffer (pH 7.4) with 280 mM sucrose and 5 mM Mg 2+ , as inner solution in tube A.…”

Robust Covalent Aptamer Strategy Enables Sensitive Detection and Enhanced Inhibition of SARS-CoV-2 Proteins

“…Aptamers, also termed as chemical antibodies, are single-stranded DNA/RNA sequences generated by applying an in vitro-directed evolution technique named as s ystematic e volution of l igands by ex ponential enrichment (SELEX) against targets of interest. − Aptamers recognize their cognate targets by folding into particular conformations. Based on the low cost, easy chemical synthesis, programmability, and compatibility to various amplification methods and high-throughput techniques, aptamers have been extensively utilized in various applications including biological detection and targeted therapeutics. − The performance of aptamers in biological detection and targeted therapy are mainly determined by their binding avidity and specificity. However, the conformation of aptamers is labile based on their flexible backbone and dynamic hydrogen bond between base pairs, and easily susceptible to environmental conditions (e.g., multiple washing), undermining the binding avidity of aptamer and the stability of aptamer–target complexes. − Therefore, aptamers usually present moderate performances in detection and therapy compared to commercial antibodies.…”

Design approaches to expand the toolkit for building cotranscriptionally encoded RNA strand displacement circuits

“…Nucleic acid-based circuits, i.e., networks of interacting nucleic acids programmed to process molecular information, are an increasingly useful tool for molecular computation with applications spanning in vitro diagnostics [1][2][3][4][5] and biosensing 6,7 to synthetic cells 8,9 and cellular computation [10][11][12][13] . Nucleic acids are an ideal substrate for building molecular circuits because predictable base pairing rules facilitate the rational design of programmable interactions.…”