Student: Marco Fiorito
Previous work has shown that the translation of mechanical forces (stresses), displacements (shear) and deformations into biochemical signals (i.e. mechanotransduction) is a pivotal factor influencing cancer cell adhesion, spread and survival in various microenvironments. For example, in vivo endothelial cells need the pulsatile strain originating from the passage of the blood pulse wave in order to establish their phenotype.
We have previously shown in vitro that mechanical shear can result in cell surface adhesion receptor activation triggering apoptosis. DHDK12 colon cancer cells were grown in 2D culture and subjected to uni-axial sinusoidal motion at 90Hz in a direction parallel to the cell surface in regular growing conditions for 4 hours. Oscillations were performed with a modal exciter rigidly linked to the cell culture plate. One control plate was left without vibration in a separate incubator to prevent vibration contamination from the vibrated plate. The strain levels induced in the cell monolayer were measured on a control cell culture plate loaded with a thin layer of agarose gel (1mm, 2g/l) and covered with liquid to simulate the medium. Shear strain images were obtained on a 7T Bruker system using a spin echo MR elastography sequence synchronized with a 90Hz vibration of the imaged plate (TE/TR=38.9/1744 ms) with 4 wave offsets, 3 directions of encoding and a 300μm3 isotropic resolution. Strain was evaluated as the maximum shear strain, i.e. the difference between the maximum and the minimum eigenvalues of the strain tensor. This particular setup yielded maximum shear strains on the order of 5.5±1.1 % in the first 300μm immediately above the plastic surface. Mind, that typical maximum shear strain levels for in-vivo MR-elastography experiments do not exceed 0.1%. As expected, shear levels were negligible in the liquid medium above the thin layer of solid medium. Vibrations were sufficient to induce cell death, as observed by the 4-5-fold increase in the count of dead cells after vibrations and effector caspase-3 activation.