3D mesenchymal cell migration is driven by anterior cellular contraction that generates an extracellular matrix prestrain

Doyle, Andrew D.; Sykora, Daniel J; Pacheco, Gustavo G.; Kutys, Matthew L.; Yamada, Kenneth M.

doi:10.1016/j.devcel.2021.02.017

Cited by 73 publications

(72 citation statements)

References 50 publications

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“…Specifically, do the border cells push on the nurse cells as they are migrating, driving a wave of local Myosin activation and stiffening of the nurse cell substrate? In other systems, such local stiffening appears to be cell-type and context specific, and can occur at the front or back of the migrating cells ( Doyle et al, 2021 ). Based on both our fixed- and live-imaging of Myosin activity, we believe the stiffening of the nurse cell substrate occurs on all sides of the border cell cluster.…”

Section: Discussionmentioning

confidence: 99%

Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

Lamb

Kaluarachchi

Lansakara

et al. 2021

eLife

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A key regulator of collective cell migrations, which drive development and cancer metastasis, is substrate stiffness. Increased substrate stiffness promotes migration and is controlled by Myosin. Using Drosophila border cell migration as a model of collective cell migration, we identify, for the first time, that the actin bundling protein Fascin limits Myosin activity in vivo. Loss of Fascin results in: increased activated Myosin on the border cells and their substrate, the nurse cells; decreased border cell Myosin dynamics; and increased nurse cell stiffness as measured by atomic force microscopy. Reducing Myosin restores on-time border cell migration in fascin mutant follicles. Further, Fascin’s actin bundling activity is required to limit Myosin activation. Surprisingly, we find that Fascin regulates Myosin activity in the border cells to control nurse cell stiffness to promote migration. Thus, these data shift the paradigm from a substrate stiffness-centric model of regulating migration, to uncover that collectively migrating cells play a critical role in controlling the mechanical properties of their substrate in order to promote their own migration. This understudied means of mechanical regulation of migration is likely conserved across contexts and organisms, as Fascin and Myosin are common regulators of cell migration.

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Section: Discussionmentioning

confidence: 99%

Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

Lamb

Kaluarachchi

Lansakara

et al. 2021

eLife

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“…While the HFF-1 and HT-1080 specifically would not be found in the same tissue, the HFF-1 represents a model human fibroblast, and the HT-1080 represents a model human fibrosarcoma cell—that is, a cancerous cell line derived from similar mesenchymal tissue. Both cell lines are commonly used in cell migration studies 27 . Each raw confocal image was spatially segmented into each of the four primary localization classes, skeletonized for quantification via ImageJ/FIJI, and analyzed to extract features most critical for discrimination (Fig.…”

Section: Resultsmentioning

confidence: 99%

Morphological features of single cells enable accurate automated classification of cancer from non-cancer cell lines

Mousavikhamene

Sykora

Mrksich

et al. 2021

Sci Rep

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Accurate cancer detection and diagnosis is of utmost importance for reliable drug-response prediction. Successful cancer characterization relies on both genetic analysis and histological scans from tumor biopsies. It is known that the cytoskeleton is significantly altered in cancer, as cellular structure dynamically remodels to promote proliferation, migration, and metastasis. We exploited these structural differences with supervised feature extraction methods to introduce an algorithm that could distinguish cancer from non-cancer cells presented in high-resolution, single cell images. In this paper, we successfully identified the features with the most discriminatory power to successfully predict cell type with as few as 100 cells per cell line. This trait overcomes a key barrier of machine learning methodologies: insufficient data. Furthermore, normalizing cell shape via microcontact printing on self-assembled monolayers enabled better discrimination of cell lines with difficult-to-distinguish phenotypes. Classification accuracy remained robust as we tested dissimilar cell lines across various tissue origins, which supports the generalizability of our algorithm.

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“…In imaging live cells, Doyle et al demonstrated the use of SDCM in their study of the migration of fibroblast and mesenchymal cells [ 63 ]. By imaging collagen using SDCM, they were able to show the migration of cells in 3D collagen constructs, proposing that mesenchymal cells generate forces on the ECM as they move through it.…”

Section: Imaging the Ecm Components: Past Present And Future Challengesmentioning

confidence: 99%

Optical Microscopy and the Extracellular Matrix Structure: A Review

Poole

Mostaço-Guidolin

2021

Cells

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Biological tissues are not uniquely composed of cells. A substantial part of their volume is extracellular space, which is primarily filled by an intricate network of macromolecules constituting the extracellular matrix (ECM). The ECM serves as the scaffolding for tissues and organs throughout the body, playing an essential role in their structural and functional integrity. Understanding the intimate interaction between the cells and their structural microenvironment is central to our understanding of the factors driving the formation of normal versus remodelled tissue, including the processes involved in chronic fibrotic diseases. The visualization of the ECM is a key factor to track such changes successfully. This review is focused on presenting several optical imaging microscopy modalities used to characterize different ECM components. In this review, we describe and provide examples of applications of a vast gamut of microscopy techniques, such as widefield fluorescence, total internal reflection fluorescence, laser scanning confocal microscopy, multipoint/slit confocal microscopy, two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG, THG), coherent anti-Stokes Raman scattering (CARS), fluorescence lifetime imaging microscopy (FLIM), structured illumination microscopy (SIM), stimulated emission depletion microscopy (STED), ground-state depletion microscopy (GSD), and photoactivated localization microscopy (PALM/fPALM), as well as their main advantages, limitations.

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3D mesenchymal cell migration is driven by anterior cellular contraction that generates an extracellular matrix prestrain

Cited by 73 publications

References 50 publications

Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

Morphological features of single cells enable accurate automated classification of cancer from non-cancer cell lines

Optical Microscopy and the Extracellular Matrix Structure: A Review

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