title: Multiwell stiffness assay for the study of cell responsiveness to cytotoxic drugs.
abstract: It is now well understood that the cell microenvironment, including the surrounding matrix, profoundly affects cell fate. This is especially true for solid tumors where, for example, matrix stiffness is believed to be an important factor in tumorogenesis. Our hypothesis is that since matrix stiffness affects cell fate, it may also be important in drug resistance. To test this hypothesis, we designed and built a multiwell polyacrylamide (PA) gel-based stiffness assay, in which the gels were coated with collagen in order to facilitate cell attachment and proliferation. This PA-based assay was used to examine the effect of stiffness on cultured cell responsiveness to cytotoxic drugs. In particular, we tested multiple cancer cell lines and their susceptibility to paclitaxel, a microtubule-targeting agent. By assessing cell proliferation, morphology, and the IC50 of the drug, we were able to establish that the stiffness affects responsiveness to cytotoxic drugs in a cell-dependent manner.
authors.affiliation: Program on Physical Biology (PPB), Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, 9000 Rockville Pike, Bldg. 9, Bethesda, Maryland, 20892. szustiak@slu.edu.
authors.forename: Silviya
authors.initials: S
authors.lastname: Zustiak
authors.forename: Ralph
authors.initials: R
authors.lastname: Nossal
authors.forename: Dan L
authors.initials: DL
authors.lastname: Sackett
mesh_terms: D000180:Acrylic Resins; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002477:Cells / Q000187:drug effects*; D055598:Chemical Phenomena; D005109:Extracellular Matrix / Q000737:chemistry*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020128:Inhibitory Concentration 50; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D000970:Antineoplastic Agents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000099166:Polyacrylamides
keywords: cancer; drug resistance; paclitaxel (Taxol®); polyacrylamide; substrate stiffness
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