Metastable amorphous precursors are emerging as valuable intermediates for the synthesis of materials with compositions and structures far from equilibrium. Recently, it was found that amorphous calcium barium carbonate (ACBC) can be converted into highly barium‐substituted “balcite,” a metastable high temperature modification of calcite with exceptional hardness. A systematic analysis ACBC (Ca1‐
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Amorphous calcium carbonate is an important precursor for biomineralization in marine organisms. Key outstanding problems include understanding the structure of amorphous calcium carbonate and rationalizing its metastability as an amorphous phase. Here we report high-quality atomistic models of amorphous calcium carbonate generated using state-of-the-art interatomic potentials to help guide fits to X-ray total scattering data. Exploiting a recently developed inversion approach, we extract from these models the effective Ca⋯Ca interaction potential governing the structure. This potential contains minima at two competing distances, corresponding to the two different ways that carbonate ions bridge Ca2+-ion pairs. We reveal an unexpected mapping to the Lennard-Jones–Gauss model normally studied in the context of computational soft matter. The empirical model parameters for amorphous calcium carbonate take values known to promote structural complexity. We thus show that both the complex structure and its resilience to crystallization are actually encoded in the geometrically frustrated effective interactions between Ca2+ions.
more » « less- Award ID(s):
- 1652237
- NSF-PAR ID:
- 10467711
- Publisher / Repository:
- Nature Chemistry
- Date Published:
- Journal Name:
- Nature Chemistry
- ISSN:
- 1755-4330
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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ABSTRACT Calcium ions (Ca2+) play key roles in various fundamental biological processes such as cell signaling and brain function. Molecular dynamics (MD) simulations have been used to study such interactions, however, the accuracy of the Ca2+models provided by the standard MD force fields has not been rigorously tested. Here, we assess the performance of the Ca2+models from the most popular classical force fields AMBER and CHARMM by computing the osmotic pressure of model compounds and the free energy of DNA–DNA interactions. In the simulations performed using the two standard models, Ca2+ions are seen to form artificial clusters with chloride, acetate, and phosphate species; the osmotic pressure of CaAc2and CaCl2solutions is a small fraction of the experimental values for both force fields. Using the standard parameterization of Ca2+ions in the simulations of Ca2+‐mediated DNA–DNA interactions leads to qualitatively wrong outcomes: both AMBER and CHARMM simulations suggest strong inter‐DNA attraction whereas, in experiment, DNA molecules repel one another. The artificial attraction of Ca2+to DNA phosphate is strong enough to affect the direction of the electric field‐driven translocation of DNA through a solid‐state nanopore. To address these shortcomings of the standard Ca2+model, we introduce a custom model of a hydrated Ca2+ion and show that using our model brings the results of the above MD simulations in quantitative agreement with experiment. Our improved model of Ca2+can be readily applied to MD simulations of various biomolecular systems, including nucleic acids, proteins and lipid bilayer membranes. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 752–763, 2016.
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Abnormal intracellular calcium dynamics in cardiomyocytes have major implications for contractility and rhythm, but compared to HFrEF, very little is known about calcium cycling in HFpEF.
We used rat models of HFpEF and HFrEF to reveal distinct differences in intracellular calcium regulation and excitation‐contraction (EC) coupling.
While HFrEF is characterized by defective EC coupling at baseline, HFpEF exhibits enhanced coupling fidelity, further aggravated by a reduction in β‐adrenergic sensitivity.
These differences in EC coupling and β‐adrenergic sensitivity may help explain why therapies that work in HFrEF are ineffective in HFpEF.
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