Abstract
Recent advances in electron microscopy have enabled the imaging of single cells in 3D at nanometer length scale resolutions. An uncharted frontier for in silico biology is the ability to simulate cellular processes using these observed geometries. Enabling such simulations requires watertight meshing of electron micrograph images into 3D volume meshes, which can then form the basis of computer simulations of such processes using numerical techniques such as the finite element method. In this paper, we describe the use of our recently rewritten mesh processing software, GAMer 2, to bridge the gap between poorly conditioned meshes generated from segmented micrographs and boundary marked tetrahedral meshes which are compatible with simulation. We demonstrate the application of a workflow using GAMer 2 to a series of electron micrographs of neuronal dendrite morphology explored at three different length scales and show that the resulting meshes are suitable for finite element simulations. This work is an important step towards making physical simulations of biological processes in realistic geometries routine. Innovations in algorithms to reconstruct and simulate cellular length scale phenomena based on emerging structural data will enable realistic physical models and advance discovery at the interface of geometry and cellular processes. We posit that a new frontier at the intersection of computational technologies and single cell biology is now open.
Highlights
Understanding structure-function relationships at cellular length scales is one of the central goals of modern cell biology
Using a workflow that consists of other opensource software along with GAMer 2, we demonstrate the process of going from electron micrographs to simulations for several scenes of increasing length scales
Wu et al imaged dendritic spines from neurons taken from the mouse cerebral cortex or nucleus accumbens using Focused-ion Beam Milling Scanning Electron Microscopy (FIB-SEM) [7]
Summary
Understanding structure-function relationships at cellular length scales (nm to μm) is one of the central goals of modern cell biology. Using these geometries as the basis of simulations provides an opportunity for the in silico animation of various cellular processes and the generation of experimentally testable hypotheses. In biological systems, the localization of molecular species is often heterogeneous [27, 28] which necessitates the need for boundary and region marking to represent this heterogeneity To realize these simulations, a workflow is necessary to go from images to high-quality and annotated 3D meshes compatible with different numerical simulation modalities. The output of GAMer 2 is a boundary marked and simulation compatible surface or volume mesh (Fig 1D and 1E) on which one can run finite elementbased biophysical simulations (Fig 1F)
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