(515d) Adsorption of miRNA on Silica Surfaces Probed with Metadynamics Simulations

Biomolecular adsorption onto silica surfaces is a ubiquitous phenomenon. Silica glass is not just common in the built environment but also in laboratory equipment and medical devices. Biomolecular adsorption to silica governs several scientifically interesting processes such as bio-preservation, chromatography, and bio-silification. However, the specific interactions between biomolecules and silica at the molecular level remain inadequately understood. Due to a limited number of experimental techniques available for probing the silica-biomolecule interface, there are considerable challenges in exploring the adsorption energy landscape and conformational preferences. However, understanding the arrangement of molecules at functional silica surfaces is crucial for designing new functional materials like chromatographic purification tags, preservation media, and non-fouling medical devices.

In this research, metadynamics (metaD) simulations were employed to investigate the adsorption behavior of a 21-nucleotide microRNA (miRNA21) onto silica surfaces under different interfacial pH conditions, solute salt concentrations, and salt species. The miRNA21 was selected because it is a cancer marker of clinical importance. Simulations yielded detailed molecular-level structures of the adsorption process. To enable exploration of various miRNA21 conformations on silica surface (adsorbed, desorbed, folded, and unfolded), a variation of metaD called parallel tempering metadynamics in the Well-Tempered ensemble (PT-metaD-WTE) was utilized. This technique allows for metaD to be applied alongside parallel tempering with a greatly reduced number of replicas. MetaD is a collective-variable (CV) based method in which a few slow conformational degrees of freedom are biased to enhance sampling. However, using more than two CVs becomes computationally expensive. Thus, PT-metaD-WTE uses thermal energy to overcome hidden energy barriers that the biased CVs do not consider.

Simulation results revealed a correlation between higher salt concentrations and increased binding strength, underscoring the crucial role of salt ions and water structuring in the adsorption phenomenon. Additionally, salt-mediated interactions between miRNA and silica were identified, indicating that the presence of a layer of cations in the electrical double layer (EDL) can mitigate repulsive energetic barriers between miRNA and the negatively charged silica surface. Furthermore, simulations demonstrated that acidic environments notably weaken the adsorption between miRNA21 and silica surfaces due to a reduction in salt-mediated interactions. Divalent cations were found to hinder adsorption compared to monovalent cations, likely due to their role in stabilizing the folded structure of miRNA21 in solution. These simulation results match previously published trends in other adsorption simulations. These findings underscore the significance of environmental conditions and salt-mediated interactions in determining the affinity of miRNA-silica adsorption. The mechanistic insights gained from this study offer valuable guidance for optimizing interactions between biomolecules and silica. Results have been compared to experimental observations of a recently developed silica-based biopreservation medium called CaRGOS and to other published experiments.