Characterization of multicellular breast tumor spheroids using image data-driven biophysical mathematical modeling

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dc.contributor.authorBowers, Haley J.en
dc.contributor.authorFannin, Emily E.en
dc.contributor.authorThomas, Alexandraen
dc.contributor.authorWeis, Jared A.en
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.date.accessioned2020-11-13T19:30:48Zen
dc.date.available2020-11-13T19:30:48Zen
dc.date.issued2020-07-14en
dc.description.abstractMulticellular tumor spheroid (MCTS) systems provide an in vitro cell culture model system which mimics many of the complexities of an in vivo solid tumor and tumor microenvironment, and are often used to study cancer cell growth and drug efficacy. Here, we present a coupled experimental-computational framework to estimate phenotypic growth and biophysical tumor microenvironment properties. This novel framework utilizes standard microscopy imaging of MCTS systems to drive a biophysical mathematical model of MCTS growth and mechanical interactions. By extending our previous in vivo mechanically-coupled reaction-diffusion modeling framework we developed a microscopy image processing framework capable of mechanistic characterization of MCTS systems. Using MDA-MB-231 breast cancer MCTS, we estimated biophysical parameters of cellular diffusion, rate of cellular proliferation, and cellular tractions forces. We found significant differences in these model-based biophysical parameters throughout the treatment time course between untreated and treated MCTS systems, whereas traditional size-based morphometric parameters were inconclusive. The proposed experimental-computational framework estimates mechanistic MCTS growth and invasion parameters with significant potential to assist in better and more precise assessment of in vitro drug efficacy through the development of computational analysis methodologies for three-dimensional cell culture systems to improve the development and evaluation of antineoplastic drugs.en
dc.description.notesNational Institutes of Health - National Cancer Institute K25CA204599 and P30CA012197. Wake Forest Baptist Medical Center Comprehensive Cancer Center Signaling and Biotechnology Program Pilot Grant.en
dc.description.sponsorshipNational Institutes of Health - National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [K25CA204599, P30CA012197]; Wake Forest Baptist Medical Center Comprehensive Cancer Center Signaling and Biotechnology Program Pilot Granten
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-020-68324-4en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.other11583en
dc.identifier.pmid32665565en
dc.identifier.urihttp://hdl.handle.net/10919/100858en
dc.identifier.volume10en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleCharacterization of multicellular breast tumor spheroids using image data-driven biophysical mathematical modelingen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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