Hydrogels scaffolds as 2D in vitro models to explore the impact of microenvironmental stiffness on lung adenocarcinoma cells

Mechanobiology aims at disclosing the functions and mechanisms by which mechanical, and architectural signals of the tissue microenvironment, control cell behaviors and cell states. Alteration in cellular mechanoperception and responsiveness is now recognized at the roots of cancer, and this is particularly well-appreciated in the context of lung adenocarcinoma. Here, adopting cutting-edge techniques from materials science, the different mechanical properties of microenvironment were precisely tuned within 2D polyacrylamide platforms over a range of pathophysiological stiffness (0.2-20 kPa). A first biophysical characterization of the effects of these platforms on normal (BEAS-2B) and tumoral lung epithelial cells (NCI-H23 and NCI-H1573) was performed. It emerged that cell ability to respond to substrate stiffness by regulating their adhesion and mechanical properties was progressively reduced with increasing cell tumorigenic potentials from BEAS-2B to NCI-H23 and metastatic NCI-H1573. Surprisingly, cell migration was less affected by both substrate stiffnesses and cell tumorigenicity, when analyzed in terms of cell speed. However, cell directionality, a parameter that describes cell ability to migrate in a persistent way without changing direction and then, to reach distant sites, was significantly increased in metastatic lung cells. This preliminary work lays the foundation for exploiting the behavior of lung adenocarcinoma cells in relationship to their mechanical microenvironment and unveil its potentiality as a diagnostic and/or prognostic and/or therapeutic.