ABSTRACT
PIEZO1 channels play a critical role in numerous physiological processes by transducing diverse mechanical stimuli into electrical and chemical signals. Recent studies underscore the importance of endogenous PIEZO1 activity and localization in regulating mechanotransduction. To enable physiologically and clinically relevant human-based studies, we genetically engineered human induced pluripotent stem cells (hiPSCs) to express a HaloTag fused to endogenous PIEZO1. Combined with super-resolution imaging, our chemogenetic approach allows precise visualization of PIEZO1 in various cell types. Further, the PIEZO1-HaloTag hiPSC technology allows non-invasive monitoring of channel activity via Ca2+-sensitive HaloTag ligands, with temporal resolution approaching that of patch clamp electrophysiology. Using lightsheet imaging of hiPSC-derived neural organoids, we also achieve molecular scale PIEZO1 imaging in three-dimensional tissue samples. Our advances offer a novel platform for studying PIEZO1 mechanotransduction in human cells and tissues, with potential for elucidating disease mechanisms and development of targeted therapeutics.
ABSTRACT
We investigate the dielectric constant and the dielectric decrement of aqueous NaCl solutions by means of molecular dynamic simulations. We thereby compare the performance of four different force fields and focus on disentangling the origin of the dielectric decrement and the influence of scaled ionic charges, as often used in nonpolarizable force fields to account for the missing dynamic polarizability in the shielding of electrostatic ion interactions. Three of the force fields showed excessive contact ion pair formation, which correlates with a reduced dielectric decrement. In spite of the fact that the scaling of charges only weakly influenced the average polarization of water molecules around an ion, the rescaling of ionic charges did influence the dielectric decrement, and a close-to-linear relation of the slope of the dielectric constant as a function of concentration with the ionic charge was found.
ABSTRACT
The rotational dynamics of an organic cation in hybrid halide perovskites is intricately linked to the phase transitions that are known to occur in these materials; however, the exact relation is not clear. We have performed detailed model studies on methylammonium lead iodide and formamidinium lead iodide to unravel the relation between rotational dynamics and phase behavior. We show that the occurrence of the phase transitions is due to a subtle interplay between dipole-dipole interactions between the organic cations, specific (hydrogen bonding) interactions between the organic cation and the lead iodide lattice, and deformation of the lead iodide lattice in reaction to the reduced rotational motion of the organic cations. This combination of factors results in phase transitions at specific temperatures, leading to the formation of large organized domains of dipoles. The latter can have significant effects on the electronic structure of these materials.
