a Schematic of the reaction-transport system in SMART. Considering the topological relationships between different cell compartments and information on reactions between species, fluxes across boundaries, and diffusion rates of individual species, SMART assembles a finite element system of equations. A single model in SMART may include both volume species (circles in inset) and surface species (rectangles in inset) that can all diffuse and react. b, Whole-cell geometry with segmented organelles from volume electron microscopy. c, Ca2+ release from the ER in a realistic geometry. For illustration, a linear molecular leak flux from the ER (jleak = νleak(cER − ci)) was assumed starting at t = 0, where jleak is the total flux, νleak is the leak permeability, and cER and ci are the Ca2+ concentrations in the ER and cytosol, respectively. This realistic ER geometry was derived from electron micrographs of dendritic spines27, and all rendering was performed in Paraview61. The whole cell schematic a was created with BioRender.com. b adapted from ref. 2, Springer Nature Ltd.
Researchers at the University of California San Diego have created and evaluated Spatial Modeling Algorithms for Reactions and Transport (SMART), a software package designed to simulate cell-signaling networks — complex molecular interactions that enable cells to respond to various environmental cues. These networks involve multiple steps and are heavily influenced by the three-dimensional structure of cells and subcellular components, making them difficult to model with existing tools. The team’s approach may benefit systems biology, pharmacology, and biomedical engineering research.
The researchers tested SMART in several biological systems at different scales. Their work spanned cell signaling in response to adhesive cues, calcium release in neurons and cardiac muscle cells, and ATP production in a detailed model of a single mitochondrion. By offering a flexible, accurate, and efficient method for modeling cell-signaling networks, the software could deepen understanding of cellular processes and inform the development of new treatments for human diseases.
The study was published in Nature Computational Science. It was led by Emmet Francis, Ph.D., an American Society for Engineering Education postdoctoral fellow, and overseen by Professor Padmini Rangamani, Ph.D. Both are affiliated with the Department of Pharmacology at UC San Diego School of Medicine and the Department of Mechanical and Aerospace Engineering at UC San Diego Jacobs School of Engineering. The initial version of SMART was written by Justin Laughlin, Ph.D., during his graduate studies in Rangamani’s group.
SMART is part of a collaboration with a research team led by Marie Rognes, Ph.D., at Simula Research Laboratory in Oslo, Norway. The project received support from several organizations, including the National Science Foundation, the Wu Tsai Human Performance Alliance, the Air Force Office of Scientific Research, the Hartwell Foundation, the Kavli Institute of Brain and Mind, the European Research Council, the Research Council of Norway, the K. G. Jebsen Center for Brain Fluid Research, and the Fulbright Foundation.
