Simulation software for researching the mysteries of the brain
The brain is a highly regulated organ that relies on the precise interactions of neurons, glial cells and the surrounding environment to function properly. One critical but often overlooked component of this environment is the extracellular space (ES), the network of microscopic fluid-filled gaps between brain cells. This space is implicated in molecular transport, cell communication and drug delivery, yet it has remained understudied for many years. Two recent discoveries have significantly increased interest in ES research. The first is the identification of the glymphatic system, a clearance pathway that removes metabolic waste, including toxic proteins like amyloid beta, implicated in Alzheimer’s disease. The second is the role ES plays in epileptic seizures and in propagating molecular signals.
Simulation software for studying the ES
Understanding the transport process of macromolecules in the ES can help study neurodegenerative diseases and neuropharmacological processes, particularly drug delivery in the central nervous system. The Human Brain Project has made tremendous strides in neuroscience but does not specifically address extracellular space modelling. Undertaken with the support of the https://ec.europa.eu/research/mariecurieactions/node_en (Marie Skłodowska-Curie Actions) (MSCA) programme, the HESSP project followed an in-silico approach to advance the field and model how substances diffuse through the extracellular space, particularly in the hippocampus. This region was chosen due to its well-defined structure, its relevance in testing diffusion hypotheses and its involvement in Alzheimer’s disease.
Addressing computational challenges
“Simulating the movement of billions of molecules is computationally demanding, so we had to overcome memory capacity limitations of existing computing resources,” explains MSCA research fellow Sergio Miguel Tomé. Towards this goal, the team developed an innovative computational tool optimally designed to simulate the diffusion of millions of particles efficiently. The so-called hybrid advanced particles simulator (HAPS) enables researchers to conduct experiments by adjusting environmental geometries, the number of released particles, and assigning diffusion coefficients to study the extracellular space.
Technical aspects of HAPS
HAPS has been designed with a user-friendly graphical interface, making it accessible to researchers and educators without programming expertise. It simulates diffusion based on Brownian motion, and through an optimised algorithm it allows particle movement tracking in three-dimensional environments. The software calculates the position of each particle at successive time points. It employs a dual level approach, one computational model for small-scale movements and another for long-range diffusion. This method enables the simulation of vast numbers of particles while maintaining high computational efficiency. As a result, HAPS overcomes hardware memory limitations that have constrained ES research.
Research and educational impact of HAPS
The software is expected to impact both academic education and neuroscientific research. A free version of HAPS will be made available to university instructors and students as an educational tool to enhance comprehension and engagement in disciplines such as neuroscience, pharmacology and computational biology. From a research perspective, HAPS will advance in silico studies on diffusion in the ES and could also be employed in drug delivery research for neurodegenerative diseases. “Simulating diffusion in complex anatomical locations requires continuous software development to integrate more detailed representations of neural structures and microenvironments,” emphasises Tomé. Future efforts will focus on optimising the software and making it more adaptable to future needs.
Keywords
HESSP, HAPS, brain, extracellular space, simulation software, neurodegenerative disease, Brownian motion, hippocampus