Department of Microsystems Engineering, Rochester Institute of Technology, 160 Lomb Memorial Drive, Rochester, NY 14623, USA.
Department of Biomedical Engineering, Rochester Institute of Technology, 160 Lomb Memorial Drive, Rochester, NY 14623, USA.
ACS Biomater Sci Eng. 2020 Feb 10;6(2):959-968. doi: 10.1021/acsbiomaterials.9b01584. Epub 2019 Dec 12.
Porous membranes are ubiquitous in cell co-culture and tissue-on-a-chip studies. These materials are predominantly chosen for their semi-permeable and size exclusion properties to restrict or permit transmigration and cell-cell communication. However, previous studies have shown pore size, spacing and orientation affect cell behavior including extracellular matrix production and migration. The mechanism behind this behavior is not fully understood. In this study, we fabricated micropatterned non-fouling polyethylene glycol (PEG) islands to mimic pore openings in order to decouple the effect of surface discontinuity from potential grip on the vertical contact area provided by pore wall edges. Similar to previous findings on porous membranes, we found that the PEG islands hindered fibronectin fibrillogenesis with cells on patterned substrates producing shorter fibrils. Additionally, cell migration speed over micropatterned PEG islands was greater than unpatterned controls, suggesting that disruption of cell-substrate interactions by PEG islands promoted a more dynamic and migratory behavior, similarly to enhanced cell migration on microporous membranes. Preferred cellular directionality during migration was nearly indistinguishable between substrates with identically patterned PEG islands and previously reported behavior over micropores of the same geometry, further confirming disruption of cell-substrate interactions as a common mechanism behind the cellular responses on these substrates. Interestingly, compared to respective controls, there were differences in cell spreading and a lower increase in migration speed over PEG islands compared prior results on micropores with identical feature size and spacing. This suggests that membrane pores not only disrupt cell-substrate interactions, but also provide additional physical factors that affect cellular response.
多孔膜在细胞共培养和芯片上组织研究中无处不在。这些材料主要因其半透性和尺寸排阻特性而被选择，以限制或允许迁移和细胞间通讯。然而，以前的研究表明，孔径、间距和方向会影响细胞行为，包括细胞外基质的产生和迁移。这种行为背后的机制尚未完全理解。在这项研究中，我们制造了微图案化的非粘连聚乙二醇（PEG）岛来模拟孔口，以将表面不连续性的影响与孔壁边缘提供的垂直接触面积的潜在抓握分离。与多孔膜上的先前发现类似，我们发现 PEG 岛阻碍了纤维连接蛋白的原纤维形成，在图案化基底上的细胞产生更短的原纤维。此外，细胞在微图案化的 PEG 岛上的迁移速度大于无图案对照，表明 PEG 岛对细胞-基底相互作用的破坏促进了更动态和迁移的行为，类似于在微孔膜上增强的细胞迁移。在迁移过程中，细胞的优先方向性在具有相同图案化 PEG 岛的基底之间几乎无法区分，并且与以前在相同几何形状的微孔上的行为相似，进一步证实了细胞-基底相互作用的破坏是这些基底上细胞反应的共同机制。有趣的是，与各自的对照相比，PEG 岛上的细胞铺展和迁移速度的增加程度存在差异，与微孔上具有相同特征尺寸和间距的先前结果相比。这表明膜孔不仅破坏细胞-基底相互作用，而且还提供了影响细胞反应的其他物理因素。
