Probing the Architecture of the Cell: Relating Intracellular Forces to Cell Geometry with High-Resolution Mechanical Imaging Techniques*

Our novel mechanical imaging tool based on atomic force microscopy (AFM) is capable of probing nanoscale structures in living cells to produce high spatial resolution mechanical images. Prior studies of cell stiffness could not produce enough mechanical contrast to study the mechanics of cell physiology at this length scale. Experimental results indicate that intracellular forces are responsible for the stiffness patterns we observe. While prior studies of cell stiffness provide qualitative insights into the relationship between intracellular forces and material properties of cells, we produce a mechanical model that quantitatively includes intracellular forces in the local nanomechanical response at the molecular level, which we also relate to cell shape. From our model, we can predict cell geometry and determine tension in intracellular structures, such as actin fiber bundles and the cell membrane. Parameters relevant to cell physiology can be obtained directly from mechanical AFM images using our model, which expands existing cell mechanical models into the molecular level.