BIOMECHANICAL STUDY OF THE MECHANICAL AND STRUCTURAL PROPERTIES OF ADHERENT CELLS

A cell is a biological complex system and its understanding requires a combination of various approaches including biomechanics. Like engineering materials, cells deform when external forces act on them. There is evidence that many normal and diseased conditions of cells are dependent on, or regulated by the way cells mechanically interact with the environment.
A major interest in cell mechanics is the regulation of cellular function by mechanical forces, which is determined by the composition and structures of cells. While the exact structural mechanisms involved in force transmission inside the cells are not well understood, computational cell modelling can yield important insights. This may contribute to build up a structure- function relationship of different adherent cell types. One approach to studying the mechanosensing processes is to understand the mechanical properties of cells’ constitutive components individually.
For this purpose, a representative 3D finite element model of a single adherent cell was developed based on the internal structures of the cytoskeleton that provide the cells with their mechanical properties. The results indicate which cytoskeleton components are targeted to respond to specific loading conditions, such as compression and stretching. More specifically, actin cortex and microtubules are targeted to respond to compressive loads, while actin bundles and microtubules are major components in maintaining cell forces during stretching.
This approach clarifies the effects of cytoskeletal heterogeneity and regional variations on the interpretation of force-deformation measurements. With a sensitivity study of the material properties of the different cellular components, the model shows how these properties differ to define cell rigidity across different cell types. Cell force is mainly affected by changes in cortex
thickness, cortex Young’s modulus and rigidity of the cytoplasm. Changes in rigidity of actin bundles and number of microtubules influence cell response to shear loads, while the number of actin bundles deeper in the interior of the cell, affect cell response to compression.
The time dependent responses observed following a power-law are remarkably similar to those reported for a variety of measurements with atomic force microscopy, suggesting this model is a consensus description of the fundamental principles defining cell mechanics. Simulations of the dynamic response of a single cell suggest that the origin of different force-relaxation times is linked to the structural architecture of the cell. The results also suggest that it is important to consider the viscoelastic properties of the cortex, other than the cytoplasm, to properly define the time-dependent response of the cell to compressive loads.
The FE single-cell model includes the three parameters defining the fundamental principles defining cell mechanics: rigidity, prestress and time-dependence deformation following a power-law behaviour. This thesis con- tributes to understand the mechanical interaction and properties across different cell components, responsible for cell behaviour, that will ultimately lead to functional adaptation or pathological conditions.