A mechanogenetic toolkit for interrogating cell signaling in space and time

Daeha Seo, Kaden M. Southard, Ji Wook Kim, Hyun Jung Lee, Justin Farlow, Jung Uk Lee, David B. Litt, Thomas Haas, A. Paul Alivisatos, Jinwoo Cheon, Zev J. Gartner, Young Wook Jun

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Tools 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 address this challenge, we synthesized magnetoplasmonic nanoparticles that can image, localize, and mechanically load targeted proteins with high spatiotemporal resolution. We demonstrate their utility by investigating the cell-surface activation of two mechanoreceptors: Notch and E-cadherin. By measuring cellular responses to a spectrum of spatial, chemical, temporal, and mechanical inputs at the single-molecule and single-cell levels, we reveal how spatial segregation and mechanical force cooperate to direct receptor activation dynamics. This generalizable technique can be used to control and understand diverse mechanosensitive processes in cell signaling.

Original languageEnglish
Pages (from-to)1507-1518
Number of pages12
JournalCell
Volume165
Issue number6
DOIs
Publication statusPublished - 2016 Jun 2

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Cell signaling
Mechanoreceptors
Chemical activation
Cadherins
Nanoparticles
Imaging techniques
Molecules
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Seo, D., Southard, K. M., Kim, J. W., Lee, H. J., Farlow, J., Lee, J. U., ... Jun, Y. W. (2016). A mechanogenetic toolkit for interrogating cell signaling in space and time. Cell, 165(6), 1507-1518. https://doi.org/10.1016/j.cell.2016.04.045
Seo, Daeha ; Southard, Kaden M. ; Kim, Ji Wook ; Lee, Hyun Jung ; Farlow, Justin ; Lee, Jung Uk ; Litt, David B. ; Haas, Thomas ; Alivisatos, A. Paul ; Cheon, Jinwoo ; Gartner, Zev J. ; Jun, Young Wook. / A mechanogenetic toolkit for interrogating cell signaling in space and time. In: Cell. 2016 ; Vol. 165, No. 6. pp. 1507-1518.
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Seo, D, Southard, KM, Kim, JW, Lee, HJ, Farlow, J, Lee, JU, Litt, DB, Haas, T, Alivisatos, AP, Cheon, J, Gartner, ZJ & Jun, YW 2016, 'A mechanogenetic toolkit for interrogating cell signaling in space and time', Cell, vol. 165, no. 6, pp. 1507-1518. https://doi.org/10.1016/j.cell.2016.04.045

A mechanogenetic toolkit for interrogating cell signaling in space and time. / Seo, Daeha; Southard, Kaden M.; Kim, Ji Wook; Lee, Hyun Jung; Farlow, Justin; Lee, Jung Uk; Litt, David B.; Haas, Thomas; Alivisatos, A. Paul; Cheon, Jinwoo; Gartner, Zev J.; Jun, Young Wook.

In: Cell, Vol. 165, No. 6, 02.06.2016, p. 1507-1518.

Research output: Contribution to journalArticle

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AU - Lee, Jung Uk

AU - Litt, David B.

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AU - Alivisatos, A. Paul

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Seo D, Southard KM, Kim JW, Lee HJ, Farlow J, Lee JU et al. A mechanogenetic toolkit for interrogating cell signaling in space and time. Cell. 2016 Jun 2;165(6):1507-1518. https://doi.org/10.1016/j.cell.2016.04.045