Mechanical influence of pressure, topography, and diffusion on cell physiology and function

Abstract

This thesis aims to explore the effects of pressure, topography, and diffusion on cellular function and physiology. Pressure is one form of mechanical stimuli that occurs naturally within a cellular microenvironment yet is largely overlooked in day to day cell culture. Here we present two different pressurized incubation chambers which allow for the study of cells under hydrostatic pressure up to 150 psi. HepG2 cells are shown to have an altered cell cycle for pressures of 14.5 psi (100 kPa). In the second part of this thesis, the effect of topography and cellular mechanics is explored. This field of research has received a lot of attention recently using photolithography based techniques to produce nano and micro scaled topographical features. Photolithography techniques have very little control over the radius of curvature of the edges so we use a buckling substrate to create periodic topographies with controlled curvatures. The C2C12 cells used for this experiment show alignment with 2 μm features after 24 hours however no alignment with 833 nm and 417 nm features until after 48 hours. In the final part of the thesis, a cell encapsulating microvascular stamp is introduced. This stamp delivers blood vessel growth factors, via diffusion, to the target tissue in order to guide blood vessel formation in the same pattern as inscribed in the stamp. To explore the mechanics behind the diffusional growth factor delivery, a finite element model was created to simulate the process. The numerical model developed in this study will help to better understand the interactions between cells, extracellular matrix, media, and the target tissue.