2017
DOI: 10.1016/j.cell.2017.06.005
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A Mechanogenetic Toolkit for Interrogating Cell Signaling in Space and Time

Abstract: SUMMARYTools capable of imaging and perturbing mechanical signaling pathways with fine spatiotemporal resolution have been elusive despite their importance in diverse cellular processes. The challenge in developing a mechanogenetic toolkit (i.e. selective and quantitative activation of genetically encoded mechanoreceptors) stems from the fact that many mechanically-activated processes are localized in space and time, yet additionally require mechanical loading to become activated. To Publisher's Disclaimer: Th… Show more

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Cited by 17 publications
(20 citation statements)
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References 29 publications
(54 reference statements)
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“…By contrast, Dll4 may cluster, but would not require clustering for activation, and therefore be able to generate sustained signaling through activation of individual ligand-receptor complexes or smaller clusters (Figures 5E and S6I). Future studies should provide a more complete understanding of the molecular and biophysical basis of encoding by directly testing the sensitivity of transendocytosis to ligand-receptor clustering and elucidating the mechanism and dynamics of the clustering process (Seo et al, 2017). …”
Section: Discussionmentioning
confidence: 99%
“…By contrast, Dll4 may cluster, but would not require clustering for activation, and therefore be able to generate sustained signaling through activation of individual ligand-receptor complexes or smaller clusters (Figures 5E and S6I). Future studies should provide a more complete understanding of the molecular and biophysical basis of encoding by directly testing the sensitivity of transendocytosis to ligand-receptor clustering and elucidating the mechanism and dynamics of the clustering process (Seo et al, 2017). …”
Section: Discussionmentioning
confidence: 99%
“…Advances in optical microscopy have been making long strides towards three-dimensional high-resolution imaging and it will be exciting to see this new technology employed for studies of immune cells 76, [163][164][165] . Genetic manipulation is more accessible and precise than ever before, and new optogenetic and nanomechanical methods offer unprecedented temporal and spatial control of manipulation of live cells 166,167 . Mathematical modelling of the cytoskeleton, for example using an active gel theory [G] 168 , has also been informative and may allow to understand counterintuitive mechanisms by which actin regulates cellular functions 169 .…”
Section: [H1] Conclusion and Outlookmentioning
confidence: 99%
“…Due to our lateral magnetic tweezer setup, the pulling force can be applied in the focal plane of conventionally used inverted microscopes 29 . Previous ensemble applications of magnetic nanoparticles have already demonstrated the potential of local control over cellular processes 15,18 . Our Block et al 19 .…”
Section: Discussionmentioning
confidence: 99%
“…Micro-to nanometer-sized magnetic particles coated with active biomolecules are introduced to the specimen to actuate mechanical, thermal, or biochemical signals. At the plasma membrane, mechano-, heat-, or clustering-sensitive receptors and ion channels can be activated using magnetic particles [15][16][17] . Usually, either large clusters or a high concentration of particles are used for ensemble measurements.…”
Section: Introductionmentioning
confidence: 99%