No abstract

DNA is a highly programmable biomolecule and has been used to construct biological circuits for different purposes. An important development of DNA circuits is to process the information on receptors on cell membranes. In this Communication, we introduce an architecture to program localized DNA-based biomolecular reaction networks on cancer cell membranes. Based on our architecture, various types of reaction networks have been experimentally demonstrated, from simple linear cascades to reaction networks of complex structures. These localized DNA-based reaction networks can be used for medical applications such as cancer cell detection. Compared to prior work on DNA circuits for evaluating cell membrane receptors, the DNA circuits made by our architecture have several major advantages including simpler design, lower leak, lower cost, and higher signal-to-background ratio.

An important achievement in the field of DNA-based computation has been the development of experimental protocols for evaluation of Boolean logic circuits. These protocols for DNA circuits generally take as inputs single-stranded DNA molecules that encode Boolean values, and via a series of DNA hybridization reactions then release ssDNA strands to indicate Boolean output values. However, most of these DNA circuit protocols are use-once only, and there remains the major challenge of designing DNA circuits to be renewable for use with multiple sets of inputs. Prior proposed schemes to make DNA gates renewable suffered from multiple problems, including waste accumulation, signal restoration, noise tolerance, and limited scalable complexity. In this work, we propose a scalable design and in silico verifications for photoregulated renewable DNA seesaw logic circuits, which after processing a given set of inputs, can be repeatedly reset to reliably process other distinct inputs. To achieve renewability, specific toeholds in the system are labeled with photoresponsive molecules such as azobenzene to modulate the effective rate constants of toehold-mediated strand displacement (TMSD) reactions. Our proposed design strategy of leveraging the collective effect of TMSD and azobenzene-mediated dehybridization may provide new perspectives on achieving synchronized and localized control of DNA hybridizations in complex and scalable reaction networks efficiently and economically. Various devices such as molecular walkers and motors could potentially be engineered reusable, be simulated and subsequently implemented using our simplified design strategy.