title: Live cell imaging in a micro-array of acoustic traps facilitates quantification of natural killer cell heterogeneity.
abstract: Natural killer (NK) cells kill virus-infected or cancer cells through the release of cytotoxic granules into a tight intercellular contact. NK cell populations comprise individual cells with varying sensitivity to distinct input signals, leading to disparate responses. To resolve this NK cell heterogeneity, we have designed a novel assay based on ultrasound-assisted cell-cell aggregation in a multiwell chip allowing high-resolution time-lapse imaging of one hundred NK-target cell interactions in parallel. Studying human NK cells' ability to kill MHC class I deficient tumor cells, we show that approximately two thirds of the NK cells display cytotoxicity, with some NK cells being particularly active, killing up to six target cells during the assay. We also report that simultaneous interaction with several susceptible target cells increases the cytotoxic responsiveness of NK cells, which could be coupled to a previously unknown regulatory mechanism with implications for NK-mediated tumor elimination.
authors: Department of Applied Physics, Albanova University Center, KTH - Royal Institute of Technology, SE-10691, Stockholm, Sweden.
authors: Athanasia E
authors: AE
authors: Christakou
authors: Mathias
authors: M
authors: Ohlin
authors: Bruno
authors: B
authors: Vanherberghen
authors: Mohammad Ali
authors: MA
authors: Khorshidi
authors: Nadir
authors: N
authors: Kadri
authors: Thomas
authors: T
authors: Frisk
authors: Martin
authors: M
authors: Wiklund
authors: Björn
authors: B
authors: Önfelt
mesh_terms: D002450:Cell Communication; D002469:Cell Separation / Q000295:instrumentation*; D002470:Cell Survival; D002478:Cells, Cultured; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005434:Flow Cytometry / Q000295:instrumentation*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000502:physiology*; D009374:Neoplasms, Experimental / Q000473:pathology / Q000503:physiopathology*; D013010:Sonication / Q000295:instrumentation*; D046888:Tissue Array Analysis / Q000295:instrumentation*