GAMer 2: A System for 3D Mesh Processing of Cellular Electron Micrographs

Abstract

Recent advances in electron microscopy have, for the first time, enabled imaging of single cells in 3D at a nanometer length scale resolution. An uncharted frontier for in silico biology is the ability to simulate cellular processes using these observed geometries. Enabling such simulations will require a system for going from electron micrographs to 3D volume meshes, which can then form the basis of computer simulations of such processes using numerical techniques such as the Finite Element Method (FEM). In this paper, we develop an end-to-end pipeline for this task by adapting and extending computer graphics mesh processing and smoothing algorithms. Our workflow makes use of our recently rewritten mesh processing software, GAMer 2, which implements several mesh conditioning algorithms and serves as a platform to connect different pipeline steps. We apply this pipeline to a series of electron micrographs of neuronal dendrite morphology explored at three different length scales and demonstrate that the resultant meshes are suitable for finite element simulations. Our pipeline, which consists of free and open-source community driven tools, is a step towards routine physical simulations of biological processes in realistic geometries. We posit that a new frontier at the intersection of computational technologies and single cell biology is now open. Innovations in algorithms to reconstruct and simulate cellular length scale phenomena based on emerging structural data will enable realistic physical models and advance discovery. Author summary3D imaging of cellular components and associated reconstruction methods have made great strides in the past decade, opening windows into the complex intraceullar organization. These advances also mean that computational tools need to be developed to work with these images not just for purposes of visualization but also for biophysical simulations. Here, we describe a pipeline that takes images from electron microscopy as input and produces smooth surface and volume meshes as output. These meshes are suitable for building high-quality finite element simulations of cellular processes modeled by ordinary and partial differential equations, bringing us closer to realizing the goal of generating high-resolution simulations of such phenomena in realistic geometries. We demonstrate the utility of this pipeline by meshing 3D reconstructions of dendritic spines, calculating 1 the curvatures of the different component membranes, and conducting finite-element simulations of reaction-diffusion equations using the generated meshes. The software tools employed in our pipeline are community driven, open source, and free. We believe that technologies such as those presented will enable a new frontier in biophysical simulations in realistic geometries.

An Open-Source Mesh Generation Platform for Biophysical Modeling Using Realistic Cellular Geometries

“…The GAMer workflow has been previously applied in several works ( 27 , 33 , 34 , 35 , 36 , 37 , 38 ). Several example applications are also described in the online GAMer 2 documentation.…”

“…Surface or volume meshes can be outputted to several common formats for use with other tools such as FEniCS ( 22 , 23 ), ParaView ( 24 ), MCell ( 25 ), and FFEA ( 26 ), among others. We note that although GAMer is designed primarily with FEM-based applications in mind, conditioned meshes of realistic geometries can also be used for geometric analysis such as the estimation of curvatures, volumes, and surface areas ( 27 ). Conditioned meshes can also be used in other tools such as MCell ( 25 ) and three-dimensional (3D) printing.…”

“…1 ) are provided in the documentation ( https://gamer.readthedocs.io/en/latest/tutorial.html ) and described in this report. Here, we will summarize the key implementation steps and refer the interested reader to ( 27 ) for technical details of the implementation.

Figure 1 Example workflow using GAMer to construct a tetrahedral domain suitable for use with finite element simulations.

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An Open Source Mesh Generation Platform for Biophysical Modeling Using Realistic Cellular Geometries

“…Collectively these tools enable the facile mathematical modeling of biological systems using realistic geometries. The GAMer workflow has been previously applied in several works (25,(31)(32)(33)(34)(35)(36). Several examples are described in the online GAMer 2 documentation.…”

“…1, are provided in the documentation and described in this report. Here we will summarize the key implementation steps and refer the interested reader to (25) for the technical details.…”