Open AccessTissue dynamics spectroscopy for phenotypic profiling of drug effects in three-dimensional culture
Author(s) -
David D. Nolte,
Ran An,
John Turek,
Kwan Jeong
Publication year - 2012
Publication title -
biomedical optics express
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.362
H-Index - 86
ISSN - 2156-7085
DOI - 10.1364/boe.3.002825
Subject(s) - phenotype , biological system , speckle pattern , drug response , computational biology , multicellular organism , biology , drug , biophysics , physics , optics , genetics , cell , pharmacology , gene
Coherence-gated dynamic light scattering captures cellular dynamics through ultra-low-frequency (0.005-5 Hz) speckle fluctuations and Doppler shifts that encode a broad range of cellular and subcellular motions. The dynamic physiological response of tissues to applied drugs is the basis for a new type of phenotypic profiling for drug screening on multicellular tumor spheroids. Volumetrically resolved tissue-response fluctuation spectrograms act as fingerprints that are segmented through feature masks into high-dimensional feature vectors. Drug-response clustering is achieved through multidimensional scaling with simulated annealing to construct phenotypic drug profiles that cluster drugs with similar responses. Hypoxic vs. normoxic tissue responses present two distinct phenotypes with differentiated responses to environmental perturbations and to pharmacological doses.