Water-Air Interface to Mimic In Vitro Tumoral Cell Migration in Complex Micro-Environments

Biosensors (Basel). 2022 Oct 3;12(10):822. doi: 10.3390/bios12100822.

Abstract

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.

Keywords: cell migration; cellular micro-environment; micro-patterned platform.

MeSH terms

  • Cell Movement
  • Extracellular Matrix* / chemistry
  • Extracellular Matrix* / metabolism
  • Humans
  • MCF-7 Cells
  • Water* / analysis

Substances

  • Water

Grants and funding

The work was supported by the strategic project Nano-Region Interreg V-A Italy-Slovenia 2014–2020, and partially funded by the Italian Ministry of University and Research through the project PRIN 2020—Touch on a chip and the project “Progetto di ricerca traslazionale e sviluppo preclinico di strategie terapeutiche innovative e predittive per l’ottimizzazione del trattamento di tumori cerebrali” by regione Friuli Venezia-Giulia (FVG).