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Bicarbonate (HCO3−) and sodium (Na+)-containing solutions contain droplets of a separate, bicarbonate-rich liquid condensed phase (LCP) that have higher concentrations of HCO3− relative to the bulk solution in which they reside. The existence and composition of the LCP droplets has been investigated by nanoparticle tracking analysis, nuclear magnetic resonance spectroscopy, refractive index measurements and X-ray pair distribution function analysis. The bicarbonate-rich LCP species is a previously unaccounted-for, ionic phenomenon which occurs even in solutions with solely monovalent cations. Its existence requires re-evaluation of models used to describe and model aqueous solution physicochemistry, especially those used to describe and model carbonate mineral formation.

Abstract Understanding the underlying processes of biomineralization is crucial to a range of disciplines allowing us to quantify the effects of climate change on marine organisms, decipher the details of paleoclimate records and advance the development of biomimetic materials. Many biological minerals form via intermediate amorphous phases, which are hard to characterize due to their transient nature and a lack of long-range order. Here, using Monte Carlo simulations constrained by X-ray and neutron scattering data together with model building, we demonstrate a method for determining the structure of these intermediates with a study of amorphous calcium carbonate (ACC) which is a precursor in the bio-formation of crystalline calcium carbonates. We find that ACC consists of highly ordered anhydrous nano-domains of approx. 2 nm that can be described as nanocrystalline. These nano-domains are held together by an interstitial net-like matrix of water molecules which generate, on the mesoscale, a heterogeneous and gel-like structure of ACC. We probed the structural stability and dynamics of our model on the nanosecond timescale by molecular dynamics simulations. These simulations revealed a gel-like and glassy nature of ACC due to the water molecules and carbonate ions in the interstitial matrix featuring pronounced orientational and translational flexibility. This allows for viscous mobility with diffusion constants four to five orders of magnitude lower than those observed in solutions. Small and ultra-small angle neutron scattering indicates a hierarchically-ordered organization of ACC across length scales that allow us, based on our nano-domain model, to build a comprehensive picture of ACC formation by cluster assembly from solution. This contribution provides a new atomic-scale understanding of ACC and provides a framework for the general exploration of biomineralization and biomimetic processes.

Abstract Creating a cellular model of Alzheimer's disease (AD) that accurately recapitulates disease pathology has been a longstanding challenge. Recent studies showed that human AD neural cells, integrated into three‐dimensional (3D) hydrogel matrix, display key features of AD neuropathology. Like in the human brain, the extracellular matrix (ECM) plays a critical role in determining the rate of neuropathogenesis in hydrogel‐based 3D cellular models. Aging, the greatest risk factor for AD, significantly alters brain ECM properties. Therefore, it is important to understand how age‐associated changes in ECM affect accumulation of pathogenic molecules, neuroinflammation, and neurodegeneration in AD patients and in vitro models. In this review, mechanistic hypotheses is presented to address the impact of the ECM properties and their changes with aging on AD and AD‐related dementias. Altered ECM characteristics in aged brains, including matrix stiffness, pore size, and composition, will contribute to disease pathogenesis by modulating the accumulation, propagation, and spreading of pathogenic molecules of AD. Emerging hydrogel‐based disease models with differing ECM properties provide an exciting opportunity to study the impact of brain ECM aging on AD pathogenesis, providing novel mechanistic insights. Understanding the role of ECM aging in AD pathogenesis should also improve modeling AD in 3D hydrogel systems.