During numerous biological processes, cell adhesion, cell migration and cell spreading are vital. These basic biological functions are regulated by the interaction of cells with their extracellular environment. To examine the morphology and mechanical changes occurring in mesenchymal stem cells cultured on a mechanically rigid substrate, atomic force microscopy and fluorescence microscopy were employed. Investigations of the cells revealed both linear and geodesic F-actin configurations. No particular cell characteristics or intra-cellular location were implicated in the appearance of the geodesic structures. However, the length of time the cells were cultured on the substrate correlated with the percentage appearance of the geodesic structures. Calculating energy dissipation from cell images acquired by dynamic mode atomic force microscopy, it was observed that the vertices of the geodesic structures had significantly higher energy dissipation compared to the linear F-actin and the glass. This supports work by Lazarides [J. Cell Biol. 68, 202-219 (1976)], who postulated that the vertices of these geodesic structures should have a greater flexibility. Our results also support predictions based on the microfilament tensegrity model. By understanding the basic principles of cell ultrastructure and cell mechanics in relation to different extracellular environments, a better understanding of physiological and pathological process will be elicited.