Nucleotides comprise small molecules that perform critical signaling roles in biological systems. Adenosine-based nucleotides, including adenosine tri-, di-, and mono-phosphate, are controlled through their rapid degradation by diphosphohydrolases and ectonucleotidases (NDAs). The interplay between nucleotide signaling and degradation is especially important in synapses formed between cells, which create signaling 'nanodomains'. Within these 'nanodomains', charged nucleotides interact with densely-packed membranes and biomolecules. While the contributions of electrostatic and steric interactions within such nanodomains are known to shape diffusion-limited reaction rates, less is understood about how these factors control the kinetics of nucleotidase activity. To quantify these factors, we utilized reaction-diffusion numerical simulations of 1) adenosine triphosphate (ATP) hydrolysis into adenosine monophosphate (AMP) and 2) AMP into adenosine (Ado) via two representative nucleotidases, CD39 and CD73. We evaluate these sequentially-coupled reactions in nanodomain geometries representative of extracellular synapses, within which we localize the nucleotidases. With this model, we find that 1) nucleotidase confinement reduces reaction rates relative to an open (bulk) system, 2) the rates of AMP and ADO formation are accelerated by restricting the diffusion of substrates away from the enzymes, and 3) nucleotidase co-localization and the presence of complementary (positive) charges to ATP enhance reaction rates, though the impact of these contributions on nucleotide pools depends on the degree to which the membrane competes for substrates. As a result, these contributions integratively control the relative concentrations and distributions of ATP and its metabolites within the junctional space. Altogether, our studies suggest that CD39 and CD73 nucleotidase activity within

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Silica-based materials including zeolites are commonly used for wide-ranging applications including separations and catalysis. Substrate transport rates in these materials can significantly influence the efficiency of such applications. Two factors that contribute to transport rates include (1) the porosity of the silicate matrix and (2) nonbonding interactions between the diffusing species and the silicate surface. These contributions generally emerge from disparate length scales, namely, “microscopic” (roughly nanometer-scale) and “macroscopic” (roughly micron-scale), respectively. Here, we develop a simulation framework to estimate the simultaneous impact of these factors on methane mass transport in silicate channels. Specifically, we develop a model of methane transport using homogenization theory to obtain transport parameters valid at length scales of hundreds to thousands of nanometers. These parameters implicitly reflect interactions taking place at fractions of a nanometer. The inputs to the homogenization analysis are data from extensive molecular dynamics simulations that incorporate atomistic-scale interactions, processed to yield local diffusion coefficients and mean force potentials. With this model, we demonstrate how nuances in silicate hydration and silica/methane interactions impact methane diffusion rates in silicate materials, including the effects of silicate surface chemistry such as the presence of silanol groups. The molecular dynamics simulations indicate that methane diffusivity at the silica surface is lower than the bulk-like rates observed at the center of channels of sufficient width. However, potentials of mean force generally evidence attractive methane/silica interactions that enhance diffusion overall. By simultaneously accounting for both of these effects, we show that the effective diffusion coefficient for the nanoporous silicate can be approximately double the value of estimates assuming fully bulk-like behavior in the channel. This study therefore demonstrates the importance of determining diffusion coefficients and potentials of mean force at an atomistic level when estimating transport properties in bulk materials. Importantly, we provide a simple homogenization framework to incorporate these molecular-scale attributes into bulk material transport estimates. This hybrid homogenization/molecular dynamics approach will be of general use for describing small-molecule transport in materials with detailed molecular interactions.

Membrane lipid composition is a critical feature of cell function, where cholesterol is a major lipid sterol component that influences the membranes physical and electrical properties. The effects of cholesterol on transport properties between adjacent to the cells, especially in junctions formed between cells is not completely understood. These junctions where substances transport and signaling is critical may be affected by modifying the cholesterol composition of the membrane in these junctional regions. Here we show how the cholesterol content in a membrane can regulate these phenomena by changing their effect on transport into and through regions between cell membranes in close proximity. Through geometric and electrostatic effects interaction with substrates, the properties of the fluid between membranes are shown to potentially enforce concentration gradients of dissolved compounds that may be biologically significant.

Silica-based materials including zeolites are commonly used for wide ranging applications including separations and catalysis. Substrate transport rates in these materials can significantly influence the efficiency of such applications. Two factors that contribute to transport rates include 1) the porosity of the silicate matrix and 2) non-bonding interactions between the diffusing species and the silicate surface. These contributions generally emerge from disparate length scales, namely 'microscopic' (roughly nanometer-scale) and 'macroscopic' (roughly micron-scale), respectively. Here, we develop a simulation framework to estimate the simultaneous impact of these factors on methane mass transport in silicate channels. Specifically, we develop a model of methane transport using homogenization theory to obtain transport parameters valid at length scales of hundreds to thousands of nanometers. These parameters implicitly reflect interactions taking place at fractions of a nanometer. The inputs to the homogenization analysis are data from extensive molecular dynamics simulations that incorporate atomistic-scale interactions, processed to yield local diffusion coefficients and mean force potentials. With this model, we demonstrate how nuances in silicate hydration and silica/methane interactions impact methane diffusion rates in silicate materials, including the effects of silicate surface chemistry such as the presence of silanol groups. The molecular dynamics simulations indicate that methane diffusivity at the silica surface is lower than the bulk-like rates observed at the center of channels of sufficient width. However, potentials of mean force generally evidence attractive methane/silica interactions that enhance diffusion overall. By simultaneously accounting for both of these effects, we show that the effective diffusion coefficient for the nanoporous silicate can be approximately double the value of estimates assuming fully bulk-like behavior in the channel. This study therefore demonstrates the importance of determining diffusion coefficients and potentials of mean force at an atomistic level when estimating transport properties in bulk materials. Importantly, we provide a simple homogenization framework to incorporate these molecular-scale attributes into bulk material transport estimates. This hybrid homogenization/molecular dynamics approach will be of general use for describing small molecule transport in materials with detailed molecular interactions.