1. Tunable mechanical properties of stent-like microscaffolds for studying cancer cell recognition of stiffness gradients
- Author
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Ferruccio Pisanello, Barbara Spagnolo, Sara Sergio, Luciana Algieri, Enrico Domenico Lemma, Marco Pisanello, Maria Addolorata Coluccia, Michele Maffia, Massimo De Vittorio, Lemma, Enrico Domenico, Sergio, Sara, Spagnolo, Barbara, Pisanello, Marco, Algieri, Luciana, Coluccia, Maria Addolorata, Maffia, Michele, De Vittorio, Massimo, and Pisanello, Ferruccio
- Subjects
0301 basic medicine ,Scaffold ,Materials science ,Atomic and Molecular Physics, and Optic ,3D scaffold ,Modulus ,Surfaces, Coatings and Film ,02 engineering and technology ,Condensed Matter Physic ,Multiphoton lithography ,Extracellular matrix ,Two-photon lithography ,03 medical and health sciences ,In vivo ,medicine ,Electrical and Electronic Engineering ,Invasivene ,Electronic, Optical and Magnetic Material ,Stiffness sensing ,technology, industry, and agriculture ,Stiffness ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,030104 developmental biology ,Cancer cell ,Surface modification ,medicine.symptom ,Stiffness gradient ,0210 nano-technology ,Biomedical engineering - Abstract
Physical and mechanical properties of extracellular matrix (ECM) have been proved to be crucial in the metastatic process. However, currently available studies on the interplay between ECM stiffness and cancer cell invasive behaviour are performed on planar assays, while the in vivo interaction takes place in three-dimensions. To take into consideration the ECM structural and mechanical complexity in the cell/structure interactions, we fabricated 3D microscaffolds through two-photon lithography (2PL) and tested how they are invaded by human colorectal adenocarcinoma (LS-174T) tumor cells, showing that it is possible to detect significant differences in cells/structure interaction when structural parameters are modified. In particular, both scaffold geometry and 2PL fabrication parameters were optimized to obtain 3D polymeric cylindrical structures with controlled Young's modulus and with linear stiffness gradients. The ability of LS-174T to migrate in the scaffolds was tested in different experimental conditions, including scaffolds functionalization and under β-catenin downregulation. It was observed that high Young's modulus scaffolds are always less invaded than softer ones, confirming the role of the 3D micro-environmental stiffness in mediating cells migration, including when specific functionalization or pharmacological treatments are performed.
- Published
- 2018