Cells under stress: An inertial-shear microfluidic determination of cell behaviour

Autor: Armistead, FJ, Gala De Pablo, J, Gadêlha, H, Peyman, SA, Evans, SD
Přispěvatelé: Guck, J
Jazyk: angličtina
Rok vydání: 2019
ISSN: 0006-3495
Popis: The deformability of a cell is the direct result of a complex interplay between the different constituent elements at the subcellular level, coupling a wide range of mechanical responses at different length-scales. Changes to the structure of these components can also alter cell phenotype, thus the critical importance of cell mechano-response for diagnostic applications. The response to mechanical stress depends strongly on the forces experienced by the cell. Here we use cell deformability in both shear-dominant and inertia-dominant microfluidic flow regimes to probe different aspects of the cell structure. In the inertial regime we follow cellular response from (visco-)elastic through plastic deformation to cell structural failure and show a significant drop in cell viability for shear stresses above > 11.8 kN/m2. Comparatively, a shear-dominant regime requires lower applied stresses to achieve higher cell strains. From this regime, deformation traces as a function of time contain a rich source of information including; maximum strain, elastic modulus and cell relaxation times and thus provide a number of markers for distinguishing cell types and potentially disease progression. These results emphasise the benefit of multiple parameter determination for improving detection and will ultimately lead to improved accuracy for diagnosis. We present results for leukemia cells (HL60) as a model circulatory cell as well as for a colorectal cancer cell line SW480 derived from primary adenocarcinoma (Dukes stage B). SW480 were also treated with the actin disrupting drug Latrunculin A (LatA), to test the sensitivity of flow regimes to the cytoskeleton. We show that the shear regime is more sensitive to cytoskeletal changes, and that large strains in the inertial-regime cannot resolve changes to the actin cytoskeleton.
Databáze: OpenAIRE