Simulations of Optical Tweezers Experiments Reveal Details of RNA Structure Unfolding

Abstract

Ca imaging techniques to visualize the spread of the impulse across the entire network of SAN cells and local Ca release dynamics within individual cells. Immunolabeling of Connexin-43 and HCN4 was employed to correlate cytoarchitecture with Ca activity. Rhythmic AP-induced Ca transients (APCTs), which correlated with APs recorded simultaneously using sharp microelectrode, were employed to monitor the impulse conduction across the SAN. The site at which the earliest APCTs occurred, identified by phase shift analysis, was between crista terminalis and superior vena cava. The APCT travels from this area across the entire SAN along curvilinear bundles of striated SAN cells rich in Connexion-43 and weak in HCN4 immunolabeling. LCRs were observed in all areas of SAN, including cells within the conduction bundles. Cells close to the APCT initiation site generated only rhythmic LCRs (without APCTs) and these LCRs preceded APCTs in the cells of the APCT-initiation area. Cells close to APCT initiation site were rich in HCN4, but essentially devoid of Connexin-43 and striations. Our results are consistent with the hypothesis that a coupled-clock system operates both within and among cells comprising the SAN network: some specialized cells generate only rhythmic LCRs that ignite adjacent cells to initiate the impulse that propagates throughout the SAN cell network.

Terahertz waves regulate the mechanical unfolding of tau pre-mRNA hairpins

“… 11 SMD simulations have been used to reduce the pathways and dynamic mechanisms of DNA, RNA, and RNA-protein biomacromolecules unfolding, such as the relationships between the mechanical unfolding process and the pull site of parallel G-quadruplex from human telomeric DNA, 12 the pathway of double-stranded RNA to single-stranded RNA molecules, 13 the unfolding behaviors of streptomycin-binding RNA aptamer under force, 14 the complexation and dissociation mechanism of small interfering RNA and PMAL carrier, 15 and the unfolding pathway of positive strand RNA turnip crinkle virus of T-shaped structure. 16 On the other hand, SMD simulation is also employed to study the stability of weak interactions between RNA and protein macromolecules, such as the minor-groove base triples formed in the mRNA pseudoknot improving the mechanical stability, 17 the additional interaction introduced by the N501Y mutation in the receptor-binding domain of spike protein strengthening the interactions between COVID-19 and its receptor ACE2, 18 and the stable base triple unfolding intermediate revealing importance in the pseudoknot-induced frameshift. 19 …”