Nanoporous silica colloidal films with molecular transport gated by aptamers responsive to small molecules

Abstract

We report the preparation of colloidal nanoporous silica films whose function mimics that of protein channels in gating the transport of small molecules across a cell membrane. Specifically, we report a means of controlling the molecular flux through colloidal nanopores that employ aptamer oligonucleotides binding to a specific organic small molecule (cocaine). These biomacromolecules have been introduced onto the nanopore surface by attaching pre-made oligonucleotides to the activated nanopore surface. The aptamers change their conformation in response to the binding events, and thus alter the free volume of the colloidal nanopores available for molecular transport.

Surface-Modified Silica Colloidal Crystals: Nanoporous Films and Membranes with Controlled Ionic and Molecular Transport

“…To complete our studies of colloidal nanoporous films modified with responsive polymers, we explored a system where the polymer conformation responds to a small molecule binding. We used a responsive DNA aptamer 46 that exhibits selective and specific binding toward cocaine. 47 The secondary structure for this 32-base aptamer possesses a three-way junction, in the middle of which there is a cavity that binds the target molecule (Figure 13).…”

“…(left) Cocaine-sensing aptamer binding to cocaine and (right) representative Fc(CH 2 OH) 2 voltammetric response for an aptamer-modified opal electrode in the absence (bottom) and in the presence of cocaine (top). Reproduced with permission from ref . Copyright 2011 Institute of Organic Chemistry and Biochemistry AS CR.…”

Nanofluidic crystals: nanofluidics in a close-packed nanoparticle array

“…Thus-induced ITR has so far been demonstrated with temperature-responsive poly(N-isopropylacrylamide) (PNIPAM) 52 and Polyalanine, 56 pH-responsive poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA), 55 and small molecule binding responsive aptamers. 57 For example, in PDMAEMA-filled nanofluidic crystal, the flux of Ru(NH 3 ) 6 3+ was shown to drop abruptly at low pHs due to the protonation (electrostatic effect) and stretching (steric effect) of polymer chains. In comparison, the neutral molecule Fc(CH 2 OH) 2 only had a ~30% drop in limiting current, which corresponded exclusively to steric hindrance of the PDMAEMA chains.…”

“…Upon the binding of cocaine, the immobilized aptamers changed to a conformation with less space occupation, which increased the effective radius of the nanochannels and led to the increased ionic fluxes through the nanofluidic crystal. 57 Based on the electrostatic effect, Lei et al 117 and Sang et al 118 demonstrated nanofluidic crystal-based biochemical sensing of biotin and human α-thrombin in low ionic concentrations (<10 −5 M), achieving a similar LOD of ~1 nM. In the work of Sang et al , upon the binding of human α-thrombin to the negatively charged aptamer-modified 540 nm nanofluidic crystal, the surface charge density of the nanoparticles increased, which led to the increase of the conductance of the nanofluidic crystal (Figure 11(a)).…”

Reversible nanovalves in inorganic materials

“…The same group also prepared aptamer-based nanovalves in silica colloidal crystals. 74 The molecular flux through aptamermodified colloidal crystals with 7.8 and 22.5 nm radius nanopores reversibly increased in the presence of cocaine, indicating conformational changes (folding) of the aptamer as a result of the cocaine binding, leading to a ca. 0.5 nm increase in the nanopore radius.…”