| Autor: |
Henslee EA; Centre for Biomedical Engineering, Department of Mechanical Engineering Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK.; Department of Engineering, Wake Forest University, Wake Downtown, Winston-Salem, NC, 27109, USA., Dunlop CM; Department of Mathematics, University of Surrey, Guildford, GU2 7XH, Surrey, UK., de Mel CM; Centre for Biomedical Engineering, Department of Mechanical Engineering Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK., Carter EA; Centre for Biomedical Engineering, Department of Mechanical Engineering Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK., Abdallat RG; Centre for Biomedical Engineering, Department of Mechanical Engineering Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK.; Department of Biomedical Engineering, Faculty of Engineering, The Hashemite University, PO Box 330127, Zarqa, 13133, Jordan., Camelliti P; School of Biosciences and Medicine, University of Surrey, Guildford, GU2 7XH, Surrey, UK., Labeed FH; Centre for Biomedical Engineering, Department of Mechanical Engineering Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK. f.labeed@surrey.ac.uk. |
| Abstrakt: |
It is known that cells grown in 3D are more tolerant to drug treatment than those grown in dispersion, but the mechanism for this is still not clear; cells grown in 3D have opportunities to develop inter-cell communication, but are also closely packed which may impede diffusion. In this study we examine methods for dielectrophoresis-based cell aggregation of both suspension and adherent cell lines, and compare the effect of various drugs on cells grown in 3D and 2D. Comparing viability of pharmacological interventions on 3D cell clusters against both suspension cells and adherent cells grown in monolayer, as well as against a unicellular organism with no propensity for intracellular communication, we suggest that 3D aggregates of adherent cells, compared to suspension cells, show a substantially different drug response to cells grown in monolayer, which increases as the IC 50 is approached. Further, a mathematical model of the system for each agent demonstrates that changes to drug response are due to inherent changes in the system of adherent cells from the 2D to 3D state. Finally, differences in the electrophysiological membrane properties of the adherent cell type suggest this parameter plays an important role in the differences found in the 3D drug response. |
