Finite element modelling of cell mechanics and cell-material interactions

Abstract

Understanding cell mechanics subjected to external stimuli is important to design microniche to direct cell migration, differentiation and proliferation. However, previous models have not elucidated the mechanisms during the mechanotransduction process. Therefore, the main objective of this thesis is to develop different types of cell models including structure-based and continuum-based models to study the cell response during interactions with external stimuli. The structure-based cell model consisting of discrete cellular components was adopted to study the cellular responses during atomic force microscope (AFM) indentation tests, which revealed the significant contribution of stress fibres (SFs) to apparent modulus. A continuum-based model has been developed to examine the effect of substrate thickness, lateral boundary and neighbouring cell on cell responses. In this model, the active behaviour of the cell was described by a SF formation model. Focal adhesion (FA) model driven by the SF contractility was implemented to account for the interactions with substrate. It has revealed that the thin layer of substrate enhanced the SF and FA formation. The SF concentration and integrin density decrease exponentially with increasing substrate thickness. Higher substrate stiffness attenuates the cell responses to thickness variation. Larger cell sizes promote the formation of SFs and enable deeper thickness sensing. Fixed lateral boundary of the substrate influences the SF and FA formation as well as the SF orientation. Soft substrate enables cells to sense the lateral displacement field created by another cell while stiff substrate hinders the cell-cell communication. Cell orients its SFs towards the neighbouring cell and could be influenced to polarize in this direction. These predictions are consistent with experimental findings. Furthermore, the physics underpinned by the modelling has improved our understanding of the substrate boundary sensing and mechanics regulated cell-cell communications. This modelling framework could be potentially adopted for rational design of biomaterials in tissue engineering.