title: A Mechanogenetic Toolkit for Interrogating Cell Signaling in Space and Time.
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.
authors.affiliation: 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.
authors.forename: Daeha
authors.initials: D
authors.lastname: Seo
authors.affiliation: 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.
authors.forename: Kaden M
authors.initials: KM
authors.lastname: Southard
authors.affiliation: 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.
authors.forename: Ji-Wook
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, University of California, San Francisco, San Francisco, CA 94115, USA.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Justin
authors.initials: J
authors.lastname: Farlow
authors.affiliation: 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.
authors.forename: Jung-Uk
authors.initials: JU
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: David B
authors.initials: DB
authors.lastname: Litt
authors.affiliation: Department of Otolaryngology, University of California, San Francisco, San Francisco, CA 94115, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haas
authors.affiliation: 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.
authors.forename: A Paul
authors.initials: AP
authors.lastname: Alivisatos
authors.affiliation: 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.
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Cheon
authors.affiliation: 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.
authors.forename: Zev J
authors.initials: ZJ
authors.lastname: Gartner
authors.affiliation: 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.
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Jun
mesh_terms: D000199:Actins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D005821:Genetic Techniques; D006801:Humans; D008465:Mechanoreceptors / Q000502:physiology; D040542:Mechanotransduction, Cellular; D053768:Metal Nanoparticles / Q000737:chemistry; D008863:Microspheres; D015336:Molecular Probe Techniques; D051880:Receptors, Notch / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D062206:Spatial Analysis; D013995:Time
chemical_list: D000199:Actins; D015820:Cadherins; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins