A Cell Mechanical Study on Adherent and Suspended Pancreatic Cancer Cells using AFM and Microfluidics

Cell mechanical responses are important in the context of physiologically relevant deformations and stresses that cells have to sustain inside the body. The cell material response to quasistatic and localized deformations, similar to those during active cell migration, is studied in the first part of this thesis. Living adherent pancreatic cells and their extracted subcellular keratin network were probed using Atomic Force Microscopy (AFM) indentation testing in order to determine if there is a significant mechanical contribution of the keratin network to living cell mechanics. It was found that the extracted keratin network elastic modulus was only 2 to 5 % of the living cell elastic modulus. No correlation of elastic moduli and keratin mesh densities was detected for living cells, whereas a huge cell-to-cell variation in the elastic moduli was present. Deformations mimicking those a cell may be subjected to during passive transport in the blood vessel system were studied in the second part of this thesis. Here, the dynamics of the same cells, but in a suspended state, was observed at high deformation rates and on a whole cell level during their transit through a microfluidic channel restriction. A novel cantilever-based method (microflap) was incorporated in the microrestrictions of a flow cell chip. For the first time, the cell mechanical response was assessed directly, and indepent of applied flow and frictional resistance, while the cell was squeezed through a microchannel restriction. Using the approximation of a uniformly loaded cantilever, the total force and the pressure exerted on the microflap by the cell can be calculated from the flap deflections