VolRoverN: Enhancing Surface and Volumetric Reconstruction for Realistic Dynamical Simulation of Cellular and Subcellular Function

Edwards, J.B.; Daniel, Eric D.; Kinney, Justin P.; Bartol, Thomas M.; Sejnowski, Terrence J.; Johnston, Daniel; Harris, Kristen M.; Bajaj, Chandrajit L.

doi:10.1007/s12021-013-9205-2

Cited by 26 publications

(27 citation statements)

References 54 publications

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“…We started with a 6 × 6 × 5 μm cube of neuropil from stratum radiatum of the hippocampus reconstructed from electron micrographs of 100 serial sections (Figure 1 , see Mishchenko et al, 2010 ; Kinney et al, 2013 ). The process of reconstruction, adjustment of extracellular space, and creation of water-tight triangulated surfaces for computer simulation is described in detail in Kinney ( 2009 ), Kinney et al ( 2013 ), and Edwards et al ( 2014 ). The reconstruction of the extent and tortuosity of the extracellular space permits accurate modeling of the time-course of diffusion of glutamate through and out of the synaptic cleft.…”

Section: Methodsmentioning

confidence: 99%

Computational reconstitution of spine calcium transients from individual proteins

Bartol

Keller

Kinney

et al. 2015

Front. Synaptic Neurosci.

266

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We have built a stochastic model in the program MCell that simulates Ca2+ transients in spines from the principal molecular components believed to control Ca2+ entry and exit. Proteins, with their kinetic models, are located within two segments of dendrites containing 88 intact spines, centered in a fully reconstructed 6 × 6 × 5 μm3 cube of hippocampal neuropil. Protein components include AMPA- and NMDA-type glutamate receptors, L- and R-type voltage-dependent Ca2+ channels, Na+/Ca2+ exchangers, plasma membrane Ca2+ ATPases, smooth endoplasmic reticulum Ca2+ ATPases, immobile Ca2+ buffers, and calbindin. Kinetic models for each protein were taken from published studies of the isolated proteins in vitro. For simulation of electrical stimuli, the time course of voltage changes in the dendritic spine was generated with the desired stimulus in the program NEURON. Voltage-dependent parameters were then continuously re-adjusted during simulations in MCell to reproduce the effects of the stimulus. Nine parameters of the model were optimized within realistic experimental limits by a process that compared results of simulations to published data. We find that simulations in the optimized model reproduce the timing and amplitude of Ca2+ transients measured experimentally in intact neurons. Thus, we demonstrate that the characteristics of individual isolated proteins determined in vitro can accurately reproduce the dynamics of experimentally measured Ca2+ transients in spines. The model will provide a test bed for exploring the roles of additional proteins that regulate Ca2+ influx into spines and for studying the behavior of protein targets in the spine that are regulated by Ca2+ influx.

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Section: Methodsmentioning

confidence: 99%

Computational reconstitution of spine calcium transients from individual proteins

Bartol

Keller

Kinney

et al. 2015

Front. Synaptic Neurosci.

266

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“…Most of our datasets have been manually segmented and corrected in software such as IMOD [34], ilastik [35], or TrackEM2 [36]. IMOD and other tools such as Contour-Tiler in VolRoverN [37] among others [38,39] have the capacity to perform contour-tiling operations to generate a preliminary surface mesh suitable for basic 3D visualization. If the end goal is visualizing the geometry of the cellular structure, then such meshing operations are often sufficient.…”

Section: Plos Computational Biologymentioning

confidence: 99%

“…In Fig 7 we compare the meshes generated by GAMer 2 with other software including TetWild [40], CGAL 3D Mesh Generation (referred to as CGAL in the subsequent text) [44][45][46], Hu et al Remesh [89], and VolRoverN [37]. For this analysis, we performed a best faith effort to use these tools using recommended default settings where possible, additional details are provided in S1 Appendix.…”

Section: Plos Computational Biologymentioning

confidence: 99%

“…VolRoverN, on the other hand, implements the Level Set Boundary-Interior-Exterior (LBIE) algorithm which employs a geometric flow. The LBIE algorithm is known to work well for spherical geometries and was designed for smoothing biomolecular meshes constructed as the union of hard spheres [37,91,92]. Given the complex geometry of the dendritic spine, VolRoverN does not preserve the geometry well.…”

Section: Plos Computational Biologymentioning

confidence: 99%

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3D mesh processing using GAMer 2 to enable reaction-diffusion simulations in realistic cellular geometries

et al. 2020

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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.

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“…Most of our datasets have been manually segmented and corrected in software such as IMOD [1], ilastik [8], or TrackEM2 [9]. IMOD and other tools such as ContourTiler in VolRoverN [10] have the capacity to perform contour-tiling operations to generate a preliminary surface mesh suitable for basic 3D visualization. These meshes, however, are often not directly suitable for physical simulations due to various mesh artifacts.…”

Section: Meshing Challengesmentioning

confidence: 99%

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

Lee

Laughlin

Beaumelle

et al. 2019

Preprint

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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.

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VolRoverN: Enhancing Surface and Volumetric Reconstruction for Realistic Dynamical Simulation of Cellular and Subcellular Function

Cited by 26 publications

References 54 publications

Computational reconstitution of spine calcium transients from individual proteins

Computational reconstitution of spine calcium transients from individual proteins

3D mesh processing using GAMer 2 to enable reaction-diffusion simulations in realistic cellular geometries

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

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