(213d) Rational Design of DNA-Based Responsive Membranes

Aptamers are functional nucleic acids capable of specifically interacting with a molecular target. The use of DNA-aptamers in stimulus-responsive membranes provides a a modular system with a degree of freedom that is not achieved with bulk polymer membranes. By simply exchanging the recognizing element (DNA-aptamer) but without changing the overall physico-chemical properties of the system, the system can be easily adapted to different targets.

It has been reported previously that single DNA-aptamers can be used as so-called “gate keepers” in nanoporous membranes where the recognition of a molecular target results in a conformational change that in turn modulates membrane permeability. The gating function of the aptamer was shown to be specific, concentration dependent, and reversible. However, such systems depended on a fine-tuning between pore size and DNA-aptamer dimensions in order to be efficient.

To overcome this limitation, we studied DNA-aptamer sandwich and hybrid structures of different compositions. These structures are scalable and to a certain extent independent of the pore size such that the flexibility in designing responsive systems is significantly increased. In absence of a molecular target, the sandwich and hybrid structures remain stable; upon exposure to the target, the structures disintegrate as the recognition of the target is energetically more favourable than the hybridization between individual DNA segments.

We employed QCM-D and MP-SPR to monitor the systematic and controlled build-up of the DNA-sandwich and hybrid structures. This permitted a rational design of the responsive membranes using less DNA material and yielded a far lower polydispersity than a one-pot self-assembly proposed in previous studies. While exposure to the target and subsequent recognition resulted in the disintegration of the sandwich and hybrid structure, it was also found that this disintegration was heavily dependent on the liquid composition. As a lesson learnt from this systematic study, it will be shown that it is indispensable to take into account basic thermodynamics when designing DNA-based responsive membranes.