Biomechanics in monitoring of anti-tumor drug effect
Cancer leads to robust changes in mechanical landscape of both cells and microenvironment. Those changes concern both mechanical properties of cells (most solid tumours cells are softer than their healthy counterparts, Lekka, 2016) and of extracellular matrix (ECM) (it stiffens like, for example, in breast cancers). These mechanical alterations are crucial for transmission of mechanical stimuli in cells in processes referred to mechanotransduction.
Impact of PDMS substrate stiffness on DU145 cells morphology in culture.
Here we would like to understand how changes in cellular deformability induced by anti-tumour drugs affect the outcome resulting from cancer treatment. Various substrates with different stiffness are applied for cell cultures aiming at mimicking physiological mechanics of tumours. Recent studies strongly indicate that studying effects of anti-tumour drugs in cells cultured on glass/plastic surfaces may lead to the appearance of artifacts (positive-false drugs action). When mechanical properties of cell culture substrates are physiological, stimulation of cells by forces of different magnitude leads to drug-resistant phenotype (Medina et al. 2019).
(A) Fluorescent images of Du145 cells cultured on PDMS of varying stiffness. (B) Impact of PDMS substrate stiffness on cytotoxicity of vinflunine in Du145 cells. Within the range of physiological stiffness (provided by softer PDMS substrates) cells become more resistible to vinflunine action.
- M. Lekka – Discrimination between normal and cancerous cells using AFM – BioNanoScience, 6(1) (2016) 65-80.
- S. H. Medina, B. Bush, M. Cam, E. Sevcik, F.W. DelRio, K.vNandy, J.P.vSchneider – Identification of a mechanogenetic link between substrate stiffness and chemotherapeutic response in breast cancer – Biomaterials, 202 (2019) 1-11.