Biology subjects

Stuber, A.

Publications and source records attributed to Stuber, A..

3 recordsLinked to original sources

bioRxiv2023

Theoretical Analysis of Divalent Cation Effects on Aptamer Recognition of Neurotransmitter Targets

Aptamer-based sensing of small molecules such as dopamine and serotonin in the brain, requires characterization of the specific aptamer sequences in solutions mimicking the in vivo environment with physiological ionic concentrations. In particular, divalent cations (Mg2+ and Ca2+) present in brain fluid, have been shown to affect the conformational dynamics of aptamers upon target recognition. Thus, for biosensors that transduce aptamer structure switching as the signal response, it is critical to interrogate the influence of divalent cations on each unique aptamer sequence. Herein, we demonstrate the potential of molecular dynamics (MD) simulations to predict the behaviour of dopamine and serotonin aptamers on sensor surfaces. The simulations enable molecular-level visualization of aptamer conformational changes that, in some cases, are significantly influenced by divalent cations. The correlations of theoretical simulations with experimental findings validate the potential for MD simulations to predict aptamer-specific behaviors on biosensors.

neuroscience↗

bioRxiv2023

Cardiac-sympathetic contractility and neural alpha-band power: cross-modal collaboration during approach-avoidance conflict

As evidence mounts that the cardiac-sympathetic system reacts to challenging cognitive settings, we ask if these responses are passive companions or if they are instead fundamentally intertwined with cognitive function. Healthy human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous neural and cardiac signals. Participants were reward-sensitive, but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters revealed that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics suggested that widening decision boundaries served to combat reward-sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically-mediated positive inotropy). We also saw evidence of conflict-specific collaboration between the neural and cardiac-sympathetic signals. Specific to states of conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signals singular influence. Cross-trial coherence analyses provided additional support for a direct role of cardiac-sympathetics in nurturing fair assessment of information streams during conflict by disrupting the prepotent reward signals. We conclude that cardiac-sympathetic activity is not a mere companion, rather it is a critical component collaborating with cognitive processes to combat reward-sensitivity during the approach-avoidance conflict.

physiology↗

bioRxiv2023

Aptamer Conformational Dynamics Modulate Neurotransmitter Sensing in Nanopores

Aptamers that undergo conformational changes upon small-molecule recognition have been shown to gate the ionic flux through nanopores by rearranging charge density within the aptamer-occluded orifice. However, mechanistic insight into such systems where biomolecular interactions are confined in nanoscale spaces, is limited. To understand the fundamental mechanisms that facilitate the detection of small-molecule analytes inside structure-switching aptamer-modified nanopores, we correlated experimental observations to theoretical models. We developed a dopamine aptamer-functionalized nanopore sensor with femtomolar detection limits and compared the sensing behavior with a serotonin sensor fabricated with the same methodology. When sensing these two neurotransmitters with comparable mass and equal charge, the sensors showed an opposite electronic behavior. This distinctive phenomenon was extensively studied using complementary experimental techniques such as quartz crystal microbalance with dissipation monitoring, in combination with theoretical assessment by the finite element method and molecular dynamic simulations. Taken together, our studies demonstrate that the sensing behavior of aptamer-modified nanopores in detecting specific small-molecule analytes correlates to the structure-switching mechanisms of individual aptamers. We believe that such investigations not only improve our understanding of the complex interactions occurring in confined nanoscale environments, but will also drive further innovations in biomimetic nanopore technologies.

neuroscience↗