Abstract
By forming attachments and contracting, cells are able to exert forces on their surroundings and infer the mechanical nature of their microenvironment. The shape, size and location of these adhesions alters in different stiffness environments. In this thesis we explore the implications of these different attachments on the cellular mechanical sensory experience.
We model cellular contraction using continuum mechanics models based in elasticity theory. We apply these in the context of the most common biophysical experiments for cellular mechanosensation, in which cells adhere to flat substrates with known mechanical properties. For the majority, we use an active stress model.
Exploiting symmetry arguments to analytically determine the deformation of a cell with an adhered ring, we investigate the effects of adhesions restricted to the cell periphery. We then consider discrete patterns of adhesion, more representative of the biological reality. Thus, we make the novel insight that the pattern of adhesion may completely alter the substrate stiffness effectively experienced by a cell. We consider which patterns of adhesion minimise the work done to the substrate and so are most energetically favourable. Combining adhesion patterns with the focussing of contractility to the cell edge, we explore the effects on cell deformation and demonstrate that the cell may use these factors to tune its energetic response. We explore potential feedback mechanisms motivated by energy constraints or as a direct response to intracellular stress, strain or deformation. Here, we exploit an active strain approach considering the mechanical effects on the whole contractile cellular network.
We argue for the integration of theoretical models with experimental design, and the need for more systematic experimental consideration of adhesion patterns and distribution of contractile elements throughout a cell before we can begin to understand the whole cell scale mechanosensory mechanisms that govern a cell’s mechanical response to its environment."