Opportunities and Challenges in Building a Spatiotemporal Multi-scale Model of the Human Pancreatic β Cell

Singla, Jitin; McClary, Kyle M.; White, Kate L.; Alber, Frank; Šali, Andrej; Stevens, Raymond C.

doi:10.1016/j.cell.2018.03.014

Cited by 60 publications

(42 citation statements)

References 92 publications

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Section: Introductionmentioning

confidence: 99%

“…Recently, biological scientists jointly appeal for building predictive spatiotemporal cell models to open new dimensions in biological research 23 . Constructing predictive models at the intersection of biology, mathematics, physics, and computer science is an effective way to perform quantitative analysis and elucidate the underlying mechanisms of complicated biological questions 23 – 25 . In this paper, a three-dimensional self-assembling model of lamellipodial branched actin network during cell migration is constructed by taking into account of five types of key proteins, i.e., filamentous actin (F-actin), Arp2/3 complex, capping protein, filamin-A and α-actinin, and their assembling interactions, e.g., filament polymerizing, Arp2/3 complex branching, capping protein-inhibiting polymerization, and actin cross-linking proteins’ binding and unbinding.…”

Section: Introductionmentioning

confidence: 99%

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Predictive assembling model reveals the self-adaptive elastic properties of lamellipodial actin networks for cell migration

et al. 2020

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Branched actin network supports cell migration through extracellular microenvironments. However, it is unknown how intracellular proteins adapt the elastic properties of the network to the highly varying extracellular resistance. Here we develop a three-dimensional assembling model to simulate the realistic self-assembling process of the network by encompassing intracellular proteins and their dynamic interactions. Combining this multiscale model with finite element method, we reveal that the network can not only sense the variation of extracellular resistance but also self-adapt its elastic properties through remodeling with intracellular proteins. Such resistance-adaptive elastic behaviours are versatile and essential in supporting cell migration through varying extracellular microenvironments. The bending deformation mechanism and anisotropic Poisson’s ratios determine why lamellipodia persistently evolve into sheet-like structures. Our predictions are confirmed by published experiments. The revealed self-adaptive elastic properties of the networks are also applicable to the endocytosis, phagocytosis, vesicle trafficking, intracellular pathogen transport and dendritic spine formation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Predictive assembling model reveals the self-adaptive elastic properties of lamellipodial actin networks for cell migration

et al. 2020

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“…This steady progression ensures that, in time, there will be a global network of interoperating data resources that enable scientific research. Given this trajectory, it is not overly optimistic to speculate that, in the next decade, it will be possible to tackle very large structure determination challenges such as the creation of a spatiotemporal model of an entire cell (Singla et al, 2018). Screenshot of the current PDB-Dev website (https://pdb-dev.wwpdb.org).…”

Section: Perspectivesmentioning

confidence: 99%

The data universe of structural biology

Berman

Vallat

Lawson

2020

IUCrJ

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The Protein Data Bank (PDB) has grown from a small data resource for crystallographers to a worldwide resource serving structural biology. The history of the growth of the PDB and the role that the community has played in developing standards and policies are described. This article also illustrates how other biophysics communities are collaborating with the worldwide PDB to create a network of interoperating data resources. This network will expand the capabilities of structural biology and enable the determination and archiving of increasingly complex structures.

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“…In combination with visible light and electrons, X-ray microscopy paves a way to a comprehensive 3D phenotyping of cells. The human cell atlas within Chan-Zuckerberg initiative and multi-scale model of the human pancreatic beta cell are two examples of such pioneering works [171]. With such need for X-ray microscopy, its future is predestined to be a new “workhorse” for 3D phenotypic analysis of cells.…”

Section: Conclusion and Summarymentioning

confidence: 99%

Imaging cell morphology and physiology using X-rays

Weinhardt

Chen

Ekman

et al. 2019

Biochemical Society Transactions

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Morphometric measurements, such as quantifying cell shape, characterizing sub-cellular organization, and probing cell-cell interactions, are fundamental in cell biology and clinical medicine. Until quite recently, the main source of morphometric data on cells has been light- and electron-based microscope images. However, a number of technological advances have propelled X-ray microscopy into becoming another source of high-quality morphometric information. Here we review the status of X-ray microscopy as a quantitative biological imaging modality. We also describe the combination of X-ray microscopy data with information from other modalities to generate polychromatic views of biological systems. For example, the amalgamation of molecular localization data, from fluorescence microscopy or spectromicroscopy, with structural information from X-ray tomography. This combination of data from the same specimen generates a more complete picture of the system than can be obtained by a single microscopy method. Such multimodal combinations greatly enhance our understanding of biology by combining physiological and morphological data to create models that more accurately reflect the complexities of life.

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Opportunities and Challenges in Building a Spatiotemporal Multi-scale Model of the Human Pancreatic β Cell

Cited by 60 publications

References 92 publications

Predictive assembling model reveals the self-adaptive elastic properties of lamellipodial actin networks for cell migration

Predictive assembling model reveals the self-adaptive elastic properties of lamellipodial actin networks for cell migration

The data universe of structural biology

Imaging cell morphology and physiology using X-rays

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