Open AccessElastography of multicellular spheroids using 3D light microscopy
Author(s) -
Devina Jaiswal,
Zoe Moscato,
Yuji Tomizawa,
Kevin P. Claffey,
Kazunori Hoshino
Publication year - 2019
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.10.002409
Subject(s) - spheroid , confocal , elastography , confocal microscopy , differential interference contrast microscopy , microscopy , materials science , fluorescence microscope , biomedical engineering , deformation (meteorology) , microscope , optics , biophysics , chemistry , fluorescence , biology , physics , composite material , medicine , radiology , ultrasound , biochemistry , in vitro
We have demonstrated a new method of 3D elastography based on 3D light microscopy and micro-scale manipulation. We used custom-built micromanipulators to apply a mechanical force onto multicellular tumor spheroids (200-300 µm in size) and recorded the induced compression with a differential interference contrast (DIC)/confocal microscope to obtain a 4D (x, y, z, and indentation steps) image sequence. Deformation analysis made through 3D pattern tracking without using fluorescence revealed 3D structural and spatial heterogeneity in tumor spheroids. We observed a 20-30 µm-sized spot of locally-induced large deformation within a tumor spheroid. We also found solid fibroblast cores formed in a tumor-fibroblast co-culture spheroid to be stiffer than surrounding cancer cells, which would not have been discovered using only conventional fluorescence. Our new method of 3D elastography may be used to better understand structural composition in multicellular spheroids through analysis of mechanical heterogeneity.