Turning catalytically active pores into active pumps.

We develop a semi-analytical model of self-diffusioosmotic transport in active pores, which includes advective transport and the inverse chemical reaction that consumes solute. In previous work [Antunes et al., Phys. Rev. Lett. 129, 188003 (2022)], we have demonstrated the existence of a spontaneous symmetry breaking in fore-aft symmetric pores that enables them to function as a micropump. We now show that this pumping transition is controlled by three timescales. Two timescales characterize advective and diffusive transport. The third timescale corresponds to how long a solute molecule resides in the pore before being consumed. Introducing asymmetry to the pore (either via the shape or the catalytic coating) reveals a second type of advection-enabled transition. In asymmetric pores, the flow rate exhibits discontinuous jumps and hysteresis loops upon tuning the parameters that control the asymmetry. This work demonstrates the interconnected roles of shape and catalytic patterning in the dynamics of active pores and shows how to design a pump for optimum performance.

Short-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents.

PURPOSE: Aging is associated with changes in glucose homeostasis related to both decreased insulin secretion and/or impaired insulin action, contributing to the high prevalence of type 2 diabetes (T2D) in the elderly population. Additionally, studies are showing that chronically high levels of circulating insulin can also lead to insulin resistance. In contrast, physical exercise has been a strategy used to improve insulin sensitivity and metabolic health. However, the molecular alterations resulting from the effects of physical exercise in the liver on age-related hyperinsulinemia conditions are not yet fully established. This study aimed to investigate the effects of 7 days of aerobic exercise on hepatic metabolism in aged hyperinsulinemic rats (i.e., Wistar and F344) and in Slc2a4+/- mice (hyperglycemic and hyperinsulinemic mice). RESULTS: Both aged models showed alterations in insulin and glucose tolerance, which were associated with essential changes in hepatic fat metabolism (lipogenesis, gluconeogenesis, and inflammation). In contrast, 7 days of physical exercise was efficient in improving whole-body glucose and insulin sensitivity, and hepatic metabolism. The Slc2a4+/- mice presented significant metabolic impairments (insulin resistance and hepatic fat accumulation) that were improved by short-term exercise training. In this scenario, high circulating insulin may be an important contributor to age-related insulin resistance and hepatic disarrangements in some specific conditions. CONCLUSION: In conclusion, our data demonstrated that short-term aerobic exercise was able to control mechanisms related to hepatic fat accumulation and insulin sensitivity in aged rodents. These effects could contribute to late-life metabolic health and prevent the development/progression of age-related T2D.

Pumping and Mixing in Active Pores.

We show both numerically and analytically that a chemically patterned active pore can act as a micro- or nanopump for fluids, even if it is fore-aft symmetric. This is possible due to a spontaneous symmetry breaking which occurs when advection rather than diffusion is the dominant mechanism of solute transport. We further demonstrate that, for pumping and tuning the flow rate, a combination of geometrical and chemical inhomogeneities is required. For certain parameter values, the flow is unsteady, and persistent oscillations with a tunable frequency appear. Finally, we find that the flow exhibits convection rolls and hence promotes mixing in the low Reynolds number regime.

Modeling of Cell-Mediated Self-Assembled Colloidal Scaffolds.

A critical step in tissue engineering is the design and synthesis of 3D biocompatible matrices (scaffolds) to support and guide the proliferation of cells and tissue growth. The most existing techniques rely on the processing of scaffolds under controlled conditions and then implanting them in vivo, with questions related to biocompatibility and implantation that are still challenging. As an alternative, it was proposed to assemble the scaffolds in loco through the self-organization of colloidal particles mediated by cells. To overcome the difficulty to test experimentally all the relevant parameters, we propose the use of large-scale numerical simulation as a tool to reach useful predictive information and to interpret experimental results. Thus, in this study, we combine experiments, particle-based simulations, and mean-field calculations to show that, in general, the size of the self-assembled scaffold scales with the cell-to-particle ratio. However, we have found an optimal value of this ratio, for which the size of the scaffold is maximal when the cell-cell adhesion is suppressed. These results suggest that the size and structure of the self-assembled scaffolds may be designed by tuning the adhesion between cells in the colloidal suspension.

Smoluchowski equations for linker-mediated irreversible aggregation.

We developed a generalized Smoluchowski framework to study linker-mediated aggregation, where linkers and particles are explicitly taken into account. We assume that the bonds between linkers and particles are irreversible, and that clustering occurs through limited diffusion aggregation. The kernel is chosen by analogy with single-component diffusive aggregation but the clusters are distinguished by their number of particles and linkers. We found that the dynamics depends on three relevant factors, all tunable experimentally: (i) the ratio of the diffusion coefficients of particles and linkers; (ii) the relative number of particles and linkers; and (iii) the maximum number of linkers that may bond to a single particle. To solve the Smoluchoski equations analytically we employ a scaling hypothesis that renders the fraction of bondable sites of a cluster independent of the size of the cluster, at each instant. We perform numerical simulations of the corresponding lattice model to test this hypothesis. We obtain results for the asymptotic limit, and the time evolution of the bonding probabilities and the size distribution of the clusters. These findings are in agreement with experimental results reported in the literature and shed light on unexplained experimental observations.

Optimal number of linkers per monomer in linker-mediated aggregation.

We study the dynamics of diffusion-limited irreversible aggregation of monomers, where bonds are mediated by linkers. We combine kinetic Monte Carlo simulations of a lattice model with a mean-field theory to study the dynamics when the diffusion of aggregates is negligible and only monomers diffuse. We find two values of the number of linkers per monomer which maximize the size of the largest aggregate. We explain the existence of the two maxima based on the distribution of linkers per monomer. This observation is well described by a simple mean-field model. We also show that a relevant parameter is the ratio of the diffusion coefficients of monomers and linkers. In particular, when this ratio is close to ten, the two maxima merge at a single maximum.