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

doi:10.1016/j.cell.2016.04.045

Title: A Mechanogenetic Toolkit for Interrogating Cell Signaling in Space and Time

Journal Article · 12 May 2016 · Cell

DOI: https://doi.org/10.1016/j.cell.2016.04.045 · OSTI ID:1545132

Seo, Daeha ^[1]; Southard, Kaden M. ^[2]; Kim, Ji-wook ^[3]; Lee, Hyun Jung ^[4]; Farlow, Justin ^[5]; Lee, Jung-uk ^[3]; Litt, David B. ^[6]; Haas, Thomas ^[4]; Alivisatos, A. Paul ^[6]; Cheon, Jinwoo ^[3]; Gartner, Zev J. ^[5]; Jun, Young-wook ^[7]

Univ. of California, San Francisco, CA (United States). Dept. of Otolaryngology; Univ. of California, Berkeley, CA (United States). Dept. of Materials Science and Engineering; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division
Univ. of California, San Francisco, CA (United States). Dept. of Otolaryngology; Univ. of California, San Francisco, CA (United States). Dept. of Pharmaceutical Chemistry
Inst. for Basic Science (IBS), Seoul (Korea, Republic of); Yonsei Univ., Seoul (Korea, Republic of)
Univ. of California, San Francisco, CA (United States). Dept. of Otolaryngology
Univ. of California, San Francisco, CA (United States). Dept. of Pharmaceutical Chemistry
Univ. of California, Berkeley, CA (United States). Dept. of Materials Science and Engineering; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division
Univ. of California, San Francisco, CA (United States). Dept. of Otolaryngology; Inst. for Basic Science (IBS), Seoul (Korea, Republic of); Yonsei Univ., Seoul (Korea, Republic of)

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 creating 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 utilized to control and understand diverse mechanosensitive processes in cell signaling.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1545132

Journal Information:: Cell, Vol. 165, Issue 6; ISSN 0092-8674

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 108 works

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