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.
Sci Rep. 2020 Sep 3;10(1):14603. doi: 10.1038/s41598-020-71265-7.
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 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.
已知与分散培养的细胞相比，三维培养的细胞对药物治疗的耐受性更高，但这一机制尚不清楚；三维培养的细胞有机会发展细胞间通讯，但也会紧密堆积，这可能会阻碍扩散。在这项研究中，我们研究了基于介电泳的悬浮和贴壁细胞系的细胞聚集方法，并比较了不同药物对三维和二维培养细胞的影响。比较了对 3D 细胞簇进行药理学干预的存活率，与悬浮细胞和单层培养的贴壁细胞以及没有细胞内通讯倾向的单细胞生物相比，我们发现与悬浮细胞相比，贴壁细胞的 3D 聚集物对细胞的药物反应有很大的不同，随着接近 IC，这种反应会增加。此外，针对每种药物的系统数学模型表明，药物反应的变化是由于从二维到三维状态的贴壁细胞系统固有的变化所致。最后，贴壁细胞类型的电生理膜特性的差异表明，该参数在 3D 药物反应中发现的差异中起着重要作用。
