SKM 2023 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 27: Computational Biophysics II

BP 27.3: Vortrag

Donnerstag, 30. März 2023, 15:30–15:45, BAR 0106

Toehold-Mediated Strand Displacement in Random Sequence Pools — •Thomas Mayer, Lukas Oesinghaus, and Friedrich Simmel — School of Natural Sciences, Department of Bioscience, TU Munich, D-85748 Garching, Germany

Toehold-mediated strand displacement (TMSD) has been used extensively for molecular sensing and computing in DNA-based molecular circuits. As these circuits grow in complexity, sequence similarity between components can lead to cross-talk causing leak, altered kinetics, or even circuit failure. For small circuits, such unwanted interactions can be designed against. In environments containing a huge number of sequences, this becomes infeasible. Therefore, a general understanding of the impact of sequence backgrounds on TMSD reactions is of great interest. Here, we investigate the impact of random DNA sequences on TMSD circuits. We begin by studying individual interfering strands and use the obtained data to build machine learning models that estimate kinetics. We then investigate the influence of pools of random strands and find that the kinetics are determined by only a small subpopulation of strongly interacting strands. Consequently, their behavior can be mimicked by a small collection of such strands. Finally, we compare two established and a novel technique that speed up TMSD reactions in random sequence pools: a threeletter alphabet, protection of toeholds by intramolecular secondary structure, or by an additional blocking strand. We expect that our insights will be useful for the construction of TMSD circuits that are robust to molecular noise.