A CutFEM Method for a Mechanistic Modelling of Astrocytic Metabolism in 3D Physiological MorphologiesFarina, Sofia ; Voorsluijs, Valerie ; et alScientific Conference (2022, June 07) Investigating neurodegenerative diseases can be done complementary through biological and computational experiments. A good computational approach describing a simplification of the reality and focusing ... [more ▼] Investigating neurodegenerative diseases can be done complementary through biological and computational experiments. A good computational approach describing a simplification of the reality and focusing only on some features of the problem can help getting insights on the field. The question addressed in our work is the role of astrocytes in neurodegeneration. These cells have two interesting characteristics that we want to investigate in our model: first, their role as metabolic mediator between neurons and blood vessels and second, their peculiar morphology. In fact, metabolic dysfunctions and morphological changes have been noticed in astrocyte affected by neuropathology. Computationally the main difficulty arising from solving a metabolic model into cellular shape comes from the complexity of the domain. The shape of astrocytes are very ramified, with thin branches and sharp edges. As shown in our previous work \cite{Farina}, a \cutfem{} \cite{Burman} approach is a suitable tool to deal with this issue. In our latest work we use real human three-dimensional astrocyte morphologies obtained via microscopy \cite{Salamanca} as domain to solve our system. The performed simulations highlight the effect of morphological changes on the system output. Suggesting that our model can be crucial in understanding the morphological-dependency in neuropathologies and that the spatial component cannot be neglected. [less ▲] Detailed reference viewed: 179 (7 UL) 3D Modelling of a Spatially Resolved Energy Metabolism in Physiological Astrocytic MorphologyFarina, Sofia ; Voorsluijs, Valerie ; et alScientific Conference (2022) Astrocytes, the most abundant cell in the central nervous system, have a star-shaped morphology and play a central role in brain homeostasis as metabolic mediators between neurons and blood vessels ... [more ▼] Astrocytes, the most abundant cell in the central nervous system, have a star-shaped morphology and play a central role in brain homeostasis as metabolic mediators between neurons and blood vessels. Recent evidence put astrocytes therefore in the focus of neurodegeneration (ND), since in case of metabolic dysfunctions as e.g. observed in Alzheimer’s disease or Parkinson’s disease, they cannot provide neurons with sufficient amount of nutrients. Furthermore, progression of ND is often accompanied by changes in astrocytic morphology further indicating the essential role of astrocytes in the brain. Despite its importance, the complex astrocytic morphology is often neglected in modelling of metabolic reactions [1]. In this study, we propose a computational model that describes cellular metabolism through a reaction-diffusion system including two fundamental pieces of information: the intracellular spatial arrangement of the reaction sites and the real, complex geometries by using the previously developed method CutFEM([2][3]). Our findings show how intracellular spatial organisation and diffusion limitation as well as the physio- logical cell shape must be taken into account to go towards biological models that are closer to reality. In particular, the spatial distribution of mitochondria notably impacts the cellular ATP : ADP ratio, which is an indicator of the energetic state of the cell. Finally, we solve our system in a 3D human astrocytic morphology and study the different spatial arrangements of the reaction sites simulating physiological and dysfunctional behaviour. In this regard, we believe, that the proposed model is a useful instrument to gain insights into the role astrocytes play in neurodegeneration. [less ▲] Detailed reference viewed: 124 (1 UL) Mechanistic modelling of astrocytic metabolism in physiological geometries reveals spatiotemporal effects potentially driving neurodegenerationFarina, Sofia ; ; Hale, Jack et alPresentation (2021, May) Detailed reference viewed: 234 (9 UL) Deterministic Limit of Intracellular Calcium SpikesVoorsluijs, Valerie ; ; et alin Physical Review Letters (2019), 122(8), 088101 In nonexcitable cells, global Ca2+ spikes emerge from the collective dynamics of clusters of Ca2+ channels that are coupled by diffusion. Current modeling approaches have opposed stochastic descriptions ... [more ▼] In nonexcitable cells, global Ca2+ spikes emerge from the collective dynamics of clusters of Ca2+ channels that are coupled by diffusion. Current modeling approaches have opposed stochastic descriptions of these systems to purely deterministic models, while both paradoxically appear compatible with experimental data. Combining fully stochastic simulations and mean-field analyses, we demonstrate that these two approaches can be reconciled. Our fully stochastic model generates spike sequences that can be seen as noise-perturbed oscillations of deterministic origin, while displaying statistical properties in agreement with experimental data. These underlying deterministic oscillations arise from a phenomenological spike nucleation mechanism. [less ▲] Detailed reference viewed: 163 (4 UL) Reconstructing stochastic attractors from nanoscale experiments on a non-equilibrium reaction; Voorsluijs, Valerie ; et alin Physical Chemistry Chemical Physics (2018), 20(33), 21302--21312 We studied the catalytic NO2(g) + H2(g)/Pt system on model platinum catalysts with nanoscale spatial resolution by means of field emission microscopy (FEM). While the surface of the catalyst is in a non ... [more ▼] We studied the catalytic NO2(g) + H2(g)/Pt system on model platinum catalysts with nanoscale spatial resolution by means of field emission microscopy (FEM). While the surface of the catalyst is in a non-reactive state at low H2 partial pressure, bursts of activity are observed when increasing this parameter. These kinetic instabilities subsequently evolve towards self-sustained periodic oscillations for a wide range of pressures. Combining time series analyses and numerical simulations of a simple reaction model, we clarify how these observations fit in the traditional classification of dynamical systems. In particular, reconstructions of the probability density around oscillating trajectories show that the experimental system defines a crater-like structure in probability space. The experimental observations thus correspond to a noise-perturbed limit cycle emerging from a nanometric reactive system. This conclusion is further supported by comparison with stochastic simulations of the proposed chemical model. The obtained results and simulations pave the way towards a better understanding of reactive nanosystems. [less ▲] Detailed reference viewed: 89 (1 UL) |
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