title: Cell-surface sensors for real-time probing of cellular environments.
abstract: The ability to explore cell signalling and cell-to-cell communication is essential for understanding cell biology and developing effective therapeutics. However, it is not yet possible to monitor the interaction of cells with their environments in real time. Here, we show that a fluorescent sensor attached to a cell membrane can detect signalling molecules in the cellular environment. The sensor is an aptamer (a short length of single-stranded DNA) that binds to platelet-derived growth factor (PDGF) and contains a pair of fluorescent dyes. When bound to PDGF, the aptamer changes conformation and the dyes come closer to each other, producing a signal. The sensor, which is covalently attached to the membranes of mesenchymal stem cells, can quantitatively detect with high spatial and temporal resolution PDGF that is added in cell culture medium or secreted by neighbouring cells. The engineered stem cells retain their ability to find their way to the bone marrow and can be monitored in vivo at the single-cell level using intravital microscopy.
authors.affiliation: Center for Regenerative Therapeutics & Department of Medicine, Brigham & Women's Hospital, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA.
authors.forename: Weian
authors.initials: W
authors.lastname: Zhao
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schafer
authors.forename: Jonghoon
authors.initials: J
authors.lastname: Choi
authors.forename: Yvonne J
authors.initials: YJ
authors.lastname: Yamanaka
authors.forename: Maria L
authors.initials: ML
authors.lastname: Lombardi
authors.forename: Suman
authors.initials: S
authors.lastname: Bose
authors.forename: Alicia L
authors.initials: AL
authors.lastname: Carlson
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Phillips
authors.forename: Weisuong
authors.initials: W
authors.lastname: Teo
authors.forename: Ilia A
authors.initials: IA
authors.lastname: Droujinine
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Cui
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
authors.forename: Jan
authors.initials: J
authors.lastname: Lammerding
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Love
authors.forename: Charles P
authors.initials: CP
authors.lastname: Lin
authors.forename: Debanjan
authors.initials: D
authors.lastname: Sarkar
authors.forename: Rohit
authors.initials: R
authors.lastname: Karnik
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Karp
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism; D015374:Biosensing Techniques / Q000295:instrumentation* / Q000379:methods*; D001854:Bone Marrow Cells / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D005456:Fluorescent Dyes; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000378:metabolism; D059010:Single-Cell Analysis / Q000295:instrumentation* / Q000379:methods*
chemical_list: D052157:Aptamers, Nucleotide; D005456:Fluorescent Dyes; D010982:Platelet-Derived Growth Factor