A distinctive role for focal adhesion proteins in three-dimensional cell motility

By S. Fraley, Yunfeng Feng, Ranjini Krishnamurthy, Dong‐hwee Kim, A. Celedon, G. Longmore, Denis Wirtz. Nature Cell Biology, 2010

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Focal adhesions are large multi-protein assemblies that form at the basal surface of cells on planar dishes, and that mediate cell signalling, force transduction and adhesion to the substratum. Although much is known about focal adhesion components in two-dimensional (2D) systems, their role in migrating cells in a more physiological three-dimensional (3D) matrix is largely unknown. Live-cell microscopy shows that for cells fully embedded in a 3D matrix, focal adhesion proteins, including vinculin, paxillin, talin, α-actinin, zyxin, VASP, FAK and p130Cas, do not form aggregates but are diffusely distributed throughout the cytoplasm. Despite the absence of detectable focal adhesions, focal adhesion proteins still modulate cell motility, but in a manner distinct from cells on planar substrates. Rather, focal adhesion proteins in matrix-embedded cells regulate cell speed and persistence by affecting protrusion activity and matrix deformation, two processes that have no direct role in controlling 2D cell speed. This study shows that membrane protrusions constitute a critical motility/matrix-traction module that drives cell motility in a 3D matrix.

Subfields: Biomedical Engineering, Cell Biology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/a7ea957174ed0bcec0c850d2be75583222310bdc

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Citations in the corpus

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity (2021, background): “Intriguingly, those diffused proteins still reserved the ability to modulate cell migration via affecting protrusion activity and matrix deformation.(213) Moreover, it is observed that the spatial confinement could lead to the retention of mechanosensitive protein YAP/TAZ in the cell cytoplasm, and ”
Deconstructing the third dimension – how 3D culture microenvironments alter cellular cues (2012, background): “Factors such as matrix stiffness and topography are likely to contribute to the recruitment of proteins to adhesion sites and might explain some of the variations observed in different 3D contexts (Harunaga and Yamada, 2011; Fraley et al., 2010; Kubow and Horwitz, 2011).”
A Review of Cell Adhesion Studies for Biomedical and Biological Applications (2015, background): “[66] reported that instead of forming aggregates in the 3D matrix, the focal adhesion proteins diffused and distributed throughout the cytoplasm and were responsible in”
In Vitro Tumor Models: Advantages, Disadvantages, Variables, and Selecting the Right Platform (2016, background): “Many avascular microfluidic devices study migration along small confined channels that are designed to mimic the quasi one-dimensional migration between fibers in the ECM (Fraley et al., 2010; Wirtz et al., 2011; Friedl et al., 2012b; Konstantopoulos et al., 2013).”
Micropatterning as a tool to decipher cell morphogenesis and functions (2010, background): “Cell adhesion on soft and on 3D substrates 3D micropatterning is more appropriate for recapitulating a physiological microenvironment than 2D micropatterning because cell behaviour is different in 2D and 3D matrices (Johnson et al., 2007; Fraley et al., 2010).”