Applications and Challenges of Machine Learning to Enable Realistic Cellular Simulations

Vasan, Ritvik; Rowan, Meagan P.; Lee, Christopher T.; Johnson, Gregory R.; Rangamani, Padmini; Holst, Michael

doi:10.3389/fphy.2019.00247

Cited by 8 publications

(6 citation statements)

References 153 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STED-FCS/fluorescence cross-correlation spectroscopy can also detect changes in intermolecular interactions ( Lanzanò et al, 2017 ). In addition to the development of new measurement techniques, molecular dynamics simulations based on experimental data will become increasingly important in the future ( Okabe, 2020a ; Reshetniak et al, 2020a ; Vasan et al, 2020 ). Spine morphology and intra-spine structures, which affect diffusion, are closely related.…”

Section: Discussionmentioning

confidence: 99%

The role of molecular diffusion within dendritic spines in synaptic function

Obashi

Taraska

Okabe

2021

Journal of General Physiology

View full text Add to dashboard Cite

Spines are tiny nanoscale protrusions from dendrites of neurons. In the cortex and hippocampus, most of the excitatory postsynaptic sites reside in spines. The bulbous spine head is connected to the dendritic shaft by a thin membranous neck. Because the neck is narrow, spine heads are thought to function as biochemically independent signaling compartments. Thus, dynamic changes in the composition, distribution, mobility, conformations, and signaling properties of molecules contained within spines can account for much of the molecular basis of postsynaptic function and regulation. A major factor in controlling these changes is the diffusional properties of proteins within this small compartment. Advances in measurement techniques using fluorescence microscopy now make it possible to measure molecular diffusion within single dendritic spines directly. Here, we review the regulatory mechanisms of diffusion in spines by local intra-spine architecture and discuss their implications for neuronal signaling and synaptic plasticity.

show abstract

Section: Discussionmentioning

confidence: 99%

The role of molecular diffusion within dendritic spines in synaptic function

Obashi

Taraska

Okabe

2021

Journal of General Physiology

View full text Add to dashboard Cite

show abstract

“…During the segmentation process, the algorithm or researcher must carefully separate boundary signal from noise. Various schemes ranging from manual tracing, thresholding and edge-detection, to deeplearning based approaches have been employed to perform image segmentation [32,33].…”

Section: Workflow Steps From Image To Modelmentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Recent ultrastructural analyses have shown that the ER is a highly dynamic, tubular network that occupies roughly 10% of the cytosolic volume and extends from the nucleus to the cell periphery 59 . Currently, geometries used in spatial models typically do not capture the complexity of the organelle ultrastructure 53 , however, advancements in meshing algorithms and modeling pipelines pave the way for more complex geometries as model inputs 60,61 . To represent the potential effect of the convoluted ultrastructure of the SR membrane, we introduce an SR flux amplification factor to our model.…”

Section: Cell Shape Changes Pm-sr Distances In 3d Two-dimensional Immentioning

confidence: 99%

Cell shape regulates subcellular organelle location to control early Ca2+ signal dynamics in vascular smooth muscle cells

Calizo

Bell

Ron

et al. 2020

Sci Rep

View full text Add to dashboard Cite

The shape of the cell is connected to its function; however, we do not fully understand underlying mechanisms by which global shape regulates a cell’s functional capabilities. Using theory, experiments and simulation, we investigated how physiologically relevant cell shape changes affect subcellular organization, and consequently intracellular signaling, to control information flow needed for phenotypic function. Vascular smooth muscle cells going from a proliferative and motile circular shape to a contractile fusiform shape show changes in the location of the sarcoplasmic reticulum, inter-organelle distances, and differential distribution of receptors in the plasma membrane. These factors together lead to the modulation of signals transduced by the M3 muscarinic receptor/Gq/PLCβ pathway at the plasma membrane, amplifying Ca2+ dynamics in the cytoplasm, and the nucleus resulting in phenotypic changes, as determined by increased activity of myosin light chain kinase in the cytoplasm and enhanced nuclear localization of the transcription factor NFAT. Taken together, our observations show a systems level phenomenon whereby global cell shape affects subcellular organization to modulate signaling that enables phenotypic changes.

show abstract

Applications and Challenges of Machine Learning to Enable Realistic Cellular Simulations

Cited by 8 publications

References 153 publications

The role of molecular diffusion within dendritic spines in synaptic function

The role of molecular diffusion within dendritic spines in synaptic function

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

Cell shape regulates subcellular organelle location to control early Ca2+ signal dynamics in vascular smooth muscle cells

Contact Info

Product

Resources

About