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  1. Article ; Online: Glioblastoma cell invasion: Go? Grow? Yes.

    Odde, David J

    Neuro-oncology

    2023  Volume 25, Issue 12, Page(s) 2163–2164

    MeSH term(s) Humans ; Glioblastoma ; Brain Neoplasms ; Cell Proliferation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Cell Movement
    Language English
    Publishing date 2023-09-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 2028601-6
    ISSN 1523-5866 ; 1522-8517
    ISSN (online) 1523-5866
    ISSN 1522-8517
    DOI 10.1093/neuonc/noad178
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5307: Show issues Location:
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  2. Article ; Online: Identifying the Mechanism of Glioblastoma Cell Migration in Mouse Brain Slices.

    Anderson, Sarah M / Odde, David J

    Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada

    2023  Volume 29, Issue 29 Suppl 1, Page(s) 1066–1067

    Language English
    Publishing date 2023-08-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 1385710-1
    ISSN 1435-8115 ; 1431-9276
    ISSN (online) 1435-8115
    ISSN 1431-9276
    DOI 10.1093/micmic/ozad067.546
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  3. Article ; Online: Multiscale models of integrins and cellular adhesions.

    Bidone, Tamara C / Odde, David J

    Current opinion in structural biology

    2023  Volume 80, Page(s) 102576

    Abstract: Computational models of integrin-based adhesion complexes have revealed important insights into the mechanisms by which cells establish connections with their external environment. However, how changes in conformation and function of individual adhesion ... ...

    Abstract Computational models of integrin-based adhesion complexes have revealed important insights into the mechanisms by which cells establish connections with their external environment. However, how changes in conformation and function of individual adhesion proteins regulate the dynamics of whole adhesion complexes remains largely elusive. This is because of the large separation in time and length scales between the dynamics of individual adhesion proteins (nanoseconds and nanometers) and the emergent dynamics of the whole adhesion complex (seconds and micrometers), and the limitations of molecular simulation approaches in extracting accurate free energies, conformational transitions, reaction mechanisms, and kinetic rates, that can inform mechanisms at the larger scales. In this review, we discuss models of integrin-based adhesion complexes and highlight their main findings regarding: (i) the conformational transitions of integrins at the molecular and macromolecular scales and (ii) the molecular clutch mechanism at the mesoscale. Lastly, we present unanswered questions in the field of modeling adhesions and propose new ideas for future exciting modeling opportunities.
    MeSH term(s) Integrins/metabolism ; Cell Adhesion/physiology ; Cell Membrane/metabolism ; Molecular Conformation ; Kinetics ; Focal Adhesions/metabolism
    Chemical Substances Integrins
    Language English
    Publishing date 2023-03-20
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 1068353-7
    ISSN 1879-033X ; 0959-440X
    ISSN (online) 1879-033X
    ISSN 0959-440X
    DOI 10.1016/j.sbi.2023.102576
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    Zs.A 3206: Show issues Location:
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  4. Article: Glioblastoma Cells Use an Integrin- and CD44-Mediated Motor-Clutch Mode of Migration in Brain Tissue.

    Anderson, Sarah M / Kelly, Marcus / Odde, David J

    Cellular and molecular bioengineering

    2024  Volume 17, Issue 2, Page(s) 121–135

    Abstract: Purpose: Glioblastoma (GBM) is an aggressive malignant brain tumor with 2 year survival rates of 6.7% (Stupp et al. in J Clin Oncol Off J Am Soc Clin Oncol 25:4127-4136, 2007; Mohammed et al. in Rep Pract Oncol Radiother 27:1026-1036, 2002). One key ... ...

    Abstract Purpose: Glioblastoma (GBM) is an aggressive malignant brain tumor with 2 year survival rates of 6.7% (Stupp et al. in J Clin Oncol Off J Am Soc Clin Oncol 25:4127-4136, 2007; Mohammed et al. in Rep Pract Oncol Radiother 27:1026-1036, 2002). One key characteristic of the disease is the ability of glioblastoma cells to migrate rapidly and spread throughout healthy brain tissue (Lefranc et al. in J Clin Oncol Off J Am Soc Clin Oncol 23:2411-2422, 2005; Hoelzinger et al. in J Natl Cancer Inst 21:1583-1593, 2007). To develop treatments that effectively target cell migration, it is important to understand the fundamental mechanism driving cell migration in brain tissue. Several models of cell migration have been proposed, including the motor-clutch, bleb-based motility, and osmotic engine models.
    Methods: Here we utilized confocal imaging to measure traction dynamics and migration speeds of glioblastoma cells in mouse organotypic brain slices to identify the mode of cell migration.
    Results: We found that nearly all cell-vasculature interactions reflected pulling, rather than pushing, on vasculature at the cell leading edge, a finding consistent with a motor-clutch mode of migration, and inconsistent with an osmotic engine model or confined bleb-based migration. Reducing myosin motor activity, a key component in the motor-clutch model, was found to decrease migration speed at high doses for all cell types including U251 and 6 low-passage patient-derived xenograft lines (3 proneural and 3 mesenchymal subtypes). Variable responses were found at low doses, consistent with a motor-clutch mode of migration which predicts a biphasic relationship between migration speed and motor-to-clutch ratio. Targeting of molecular clutches including integrins and CD44 slowed migration of U251 cells.
    Conclusions: Overall we find that glioblastoma cell migration is most consistent with a motor-clutch mechanism to migrate through brain tissue ex vivo, and that both integrins and CD44, as well as myosin motors, play an important role in constituting the adhesive clutch.
    Supplementary information: The online version contains supplementary material available at 10.1007/s12195-024-00799-x.
    Language English
    Publishing date 2024-03-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2416037-4
    ISSN 1865-5033 ; 1865-5025
    ISSN (online) 1865-5033
    ISSN 1865-5025
    DOI 10.1007/s12195-024-00799-x
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  5. Article: Glioblastoma cells use an integrin- and CD44-mediated motor-clutch mode of migration in brain tissue.

    Anderson, Sarah M / Kelly, Marcus / Odde, David J

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Glioblastoma (GBM) is an aggressive malignant brain tumor with 2-year survival rates of 6.7% [1], [2]. One key characteristic of the disease is the ability of glioblastoma cells to migrate rapidly and spread throughout healthy brain tissue[3], [4]. To ... ...

    Abstract Glioblastoma (GBM) is an aggressive malignant brain tumor with 2-year survival rates of 6.7% [1], [2]. One key characteristic of the disease is the ability of glioblastoma cells to migrate rapidly and spread throughout healthy brain tissue[3], [4]. To develop treatments that effectively target cell migration, it is important to understand the fundamental mechanism driving cell migration in brain tissue. Here we utilized confocal imaging to measure traction dynamics and migration speeds of glioblastoma cells in mouse organotypic brain slices to identify the mode of cell migration. Through imaging cell-vasculature interactions and utilizing drugs, antibodies, and genetic modifications to target motors and clutches, we find that glioblastoma cell migration is most consistent with a motor-clutch mechanism to migrate through brain tissue
    Language English
    Publishing date 2023-10-25
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.23.563458
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  6. Article ; Online: Optimal cell traction forces in a generalized motor-clutch model.

    Alonso-Matilla, Roberto / Provenzano, Paolo P / Odde, David J

    Biophysical journal

    2023  Volume 122, Issue 16, Page(s) 3369–3385

    Abstract: Cells exert forces on mechanically compliant environments to sense stiffness, migrate, and remodel tissue. Cells can sense environmental stiffness via myosin-generated pulling forces acting on F-actin, which is in turn mechanically coupled to the ... ...

    Abstract Cells exert forces on mechanically compliant environments to sense stiffness, migrate, and remodel tissue. Cells can sense environmental stiffness via myosin-generated pulling forces acting on F-actin, which is in turn mechanically coupled to the environment via adhesive proteins, akin to a clutch in a drivetrain. In this "motor-clutch" framework, the force transmitted depends on the complex interplay of motor, clutch, and environmental properties. Previous mean-field analysis of the motor-clutch model identified the conditions for optimal stiffness for maximal force transmission via a dimensionless number that combines motor-clutch parameters. However, in this and other previous mean-field analyses, the motor-clutch system is assumed to have balanced motors and clutches and did not consider force-dependent clutch reinforcement and catch bond behavior. Here, we generalize the motor-clutch analytical framework to include imbalanced motor-clutch regimes, with clutch reinforcement and catch bonding, and investigate optimality with respect to all parameters. We found that traction force is strongly influenced by clutch stiffness, and we discovered an optimal clutch stiffness that maximizes traction force, suggesting that cells could tune their clutch mechanical properties to perform a specific function. The results provide guidance for maximizing the accuracy of cell-generated force measurements via molecular tension sensors by designing their mechanosensitive linker peptide to be as stiff as possible. In addition, we found that, on rigid substrates, the mean-field analysis identifies optimal motor properties, suggesting that cells could regulate their myosin repertoire and activity to maximize force transmission. Finally, we found that clutch reinforcement shifts the optimum substrate stiffness to larger values, whereas the optimum substrate stiffness is insensitive to clutch catch bond properties. Overall, our work reveals novel features of the motor-clutch model that can affect the design of molecular tension sensors and provide a generalized analytical framework for predicting and controlling cell adhesion and migration in immunotherapy and cancer.
    MeSH term(s) Biomechanical Phenomena ; Traction ; Actins/metabolism ; Actin Cytoskeleton/metabolism ; Cell Adhesion
    Chemical Substances Actins
    Language English
    Publishing date 2023-07-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2023.07.012
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    Zs.A 235: Show issues Location:
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    Zs.MO 2: Show issues

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  7. Article ; Online: Correction to: Atomistic Basis of Microtubule Dynamic Instability Assessed Via Multiscale Modeling.

    Hemmat, Mahya / Odde, David J

    Annals of biomedical engineering

    2021  Volume 49, Issue 9, Page(s) 2672

    Language English
    Publishing date 2021-08-25
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 185984-5
    ISSN 1573-9686 ; 0191-5649 ; 0090-6964
    ISSN (online) 1573-9686
    ISSN 0191-5649 ; 0090-6964
    DOI 10.1007/s10439-021-02830-y
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    Zs.A 1018: Show issues Location:
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  8. Article ; Online: Atomistic Basis of Microtubule Dynamic Instability Assessed Via Multiscale Modeling.

    Hemmat, Mahya / Odde, David J

    Annals of biomedical engineering

    2021  Volume 49, Issue 7, Page(s) 1716–1734

    Abstract: Microtubule "dynamic instability," the abrupt switching from assembly to disassembly caused by the hydrolysis of GTP to GDP within the β subunit of the αβ-tubulin heterodimer, is necessary for vital cellular processes such as mitosis and migration. ... ...

    Abstract Microtubule "dynamic instability," the abrupt switching from assembly to disassembly caused by the hydrolysis of GTP to GDP within the β subunit of the αβ-tubulin heterodimer, is necessary for vital cellular processes such as mitosis and migration. Despite existing high-resolution structural data, the key mechanochemical differences between the GTP and GDP states that mediate dynamic instability behavior remain unclear. Starting with a published atomic-level structure as an input, we used multiscale modeling to find that GTP hydrolysis results in both longitudinal bond weakening (~ 4 k
    MeSH term(s) Guanosine Diphosphate/chemistry ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/chemistry ; Guanosine Triphosphate/metabolism ; Microtubules/chemistry ; Molecular Dynamics Simulation ; Tubulin/chemistry ; Tubulin/metabolism
    Chemical Substances Tubulin ; Guanosine Diphosphate (146-91-8) ; Guanosine Triphosphate (86-01-1)
    Language English
    Publishing date 2021-02-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 185984-5
    ISSN 1573-9686 ; 0191-5649 ; 0090-6964
    ISSN (online) 1573-9686
    ISSN 0191-5649 ; 0090-6964
    DOI 10.1007/s10439-020-02715-6
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    Zs.A 1018: Show issues Location:
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  9. Article ; Online: Photoresponsive Hydrogels for Studying Mechanotransduction of Cells.

    Park, Keun-Young / Odde, David J / Distefano, Mark D

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2600, Page(s) 133–153

    Abstract: Hydrogels are important platform materials for in vitro cellular studies. Mechanistic studies on durotaxis, the directional movement of a cell affected by a spatial gradient of stiffness of the underlying substrate, requires materials such as ... ...

    Abstract Hydrogels are important platform materials for in vitro cellular studies. Mechanistic studies on durotaxis, the directional movement of a cell affected by a spatial gradient of stiffness of the underlying substrate, requires materials such as polyacrylamide, polyethylene glycol, or PDMS, in which the stiffness can be controlled in a spatiotemporal manner. Here, we describe the synthesis of an o-nitrobenzyl-based photocleavable cross-linker and its incorporation into a polyacrylamide hydrogel to render it photoresponsive. Precise control over the physical properties of the gel allows observation of glioblastoma durotaxis under surface stiffness conditions relevant to the actual brain environment.
    MeSH term(s) Humans ; Hydrogels/chemistry ; Extracellular Matrix/metabolism ; Mechanotransduction, Cellular/physiology ; Polyethylene Glycols/analysis ; Glioblastoma/metabolism
    Chemical Substances Hydrogels ; Polyethylene Glycols (3WJQ0SDW1A)
    Language English
    Publishing date 2022-12-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2851-5_9
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  10. Article ; Online: Emerging technologies in mechanotransduction research.

    Shamsan, Ghaidan A / Odde, David J

    Current opinion in chemical biology

    2019  Volume 53, Page(s) 125–130

    Abstract: Mechanotransduction research focuses on understanding how cells sense and respond to mechanical stimuli by converting mechanical signals into biochemical and biological responses. Cells have been shown to respond to mechanical stimuli through specialized ...

    Abstract Mechanotransduction research focuses on understanding how cells sense and respond to mechanical stimuli by converting mechanical signals into biochemical and biological responses. Cells have been shown to respond to mechanical stimuli through specialized biological machinery such as adhesion complexes. Research in the last two decades helped in identifying key components of cellular mechanotransduction. In recent years, integrated approaches, which are highlighted here, are emerging to provide new insights into the mechanistic and theoretical underpinnings of mechanotransduction. In particular, mathematical modeling has helped elucidate the mechanism underlining ligand spacing and distribution sensing, as well as sensing viscoelastic properties of the extracellular matrix. In addition, molecular tension sensors have helped dissect the forces involved in mechanotransduction at high spatial and temporal resolutions.
    MeSH term(s) Animals ; Humans ; Mechanotransduction, Cellular ; Models, Biological
    Language English
    Publishing date 2019-10-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1439176-4
    ISSN 1879-0402 ; 1367-5931
    ISSN (online) 1879-0402
    ISSN 1367-5931
    DOI 10.1016/j.cbpa.2019.08.002
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