Department of Physics, University of Trieste, 34127 Trieste, Italy.
IOM-CNR, Institute of Materials Foundry-National Research Council, 34149 Trieste, Italy.
Biosensors (Basel). 2022 Oct 3;12(10):822. doi: 10.3390/bios12100822.
The long-known role of cell migration in physiological and pathological contexts still requires extensive research to be fully understood, mainly because of the intricate interaction between moving cells and their surroundings. While conventional assays fail to capture this complexity, recently developed 3D platforms better reproduce the cellular micro-environment, although often requiring expensive and time-consuming imaging approaches. To overcome these limitations, we developed a novel approach based on 2D micro-patterned substrates, compatible with conventional microscopy analysis and engineered to create micro-gaps with a length of 150 µm and a lateral size increasing from 2 to 8 µm, where a curved water-air interface is created on which cells can adhere, grow, and migrate. The resulting hydrophilic/hydrophobic interfaces, variable surface curvatures, spatial confinements, and size values mimic the complex micro-environment typical of the extracellular matrix in which aggressive cancer cells proliferate and migrate. The new approach was tested with two breast cancer cell lines with different invasive properties. We observed that invasive cells (MDA-MB-231) can align along the pattern and modify both their morphology and their migration rate according to the size of the water meniscus, while non-invasive cells (MCF-7) are only slightly respondent to the surrounding micro-environment. Moreover, the selected pattern highlighted a significative matrix deposition process connected to cell migration. Although requiring further optimizations, this approach represents a promising tool to investigate cell migration in complex environments.
细胞迁移在生理和病理环境中的长期作用仍需要广泛的研究才能充分理解，主要是因为移动细胞及其周围环境之间的复杂相互作用。虽然传统的测定方法无法捕捉到这种复杂性，但最近开发的 3D 平台更好地再现了细胞的微环境，但通常需要昂贵且耗时的成像方法。为了克服这些限制，我们开发了一种基于 2D 微图案化基底的新方法，该方法与传统的显微镜分析兼容，并设计成创建长度为 150 µm 且侧向尺寸从 2 到 8 µm 逐渐增大的微间隙，其中在水-气界面上形成弯曲界面，细胞可以在该界面上附着、生长和迁移。由此产生的亲水/疏水界面、可变的表面曲率、空间限制和尺寸值模拟了富含细胞外基质的复杂微环境，侵袭性癌细胞在该环境中增殖和迁移。我们使用两种具有不同侵袭特性的乳腺癌细胞系对新方法进行了测试。我们观察到侵袭性细胞（MDA-MB-231）可以根据水弯月面的大小沿着图案排列，并根据水弯月面的大小改变其形态和迁移率，而非侵袭性细胞（MCF-7）对周围微环境的响应则很轻微。此外，所选图案突出了与细胞迁移相关的显著基质沉积过程。尽管需要进一步优化，但这种方法代表了研究复杂环境中细胞迁移的有前途的工具。
