Format

Send to

Choose Destination
Cell. 2016 Jun 2;165(6):1507-1518. doi: 10.1016/j.cell.2016.04.045. Epub 2016 May 12.

A Mechanogenetic Toolkit for Interrogating Cell Signaling in Space and Time.

Author information

1
Department of Otolaryngology, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Chemistry and Department of Materials Sciences and Engineering, University of California, Berkeley, Berkeley, CA 94720, USA; Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Kavli Energy NanoScience Institute, University of California, Berkeley and Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
2
Department of Otolaryngology, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
3
Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea; Yonsei-IBS Institute, Yonsei University, Seoul 03722, Republic of Korea; Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea.
4
Department of Otolaryngology, University of California, San Francisco, San Francisco, CA 94115, USA.
5
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
6
Department of Chemistry and Department of Materials Sciences and Engineering, University of California, Berkeley, Berkeley, CA 94720, USA; Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Kavli Energy NanoScience Institute, University of California, Berkeley and Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
7
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: zev.gartner@ucsf.edu.
8
Department of Otolaryngology, University of California, San Francisco, San Francisco, CA 94115, USA; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea; Yonsei-IBS Institute, Yonsei University, Seoul 03722, Republic of Korea. Electronic address: young-wook.jun@ucsf.edu.

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. VIDEO ABSTRACT.

PMID:
27180907
PMCID:
PMC4892966
DOI:
10.1016/j.cell.2016.04.045
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center