Relating Local Nanomechanical Response of Cells to Intracellular Forces and Cell Morphology

Abstract

Mechanical processes regulate cell physiology primarily at the molecular level, but current techniques have difficulty achieving mechanical contrast at molecular length scales. We recently developed an AFM-based tool that can probe mechanical properties of living cells with nanoscale resolution. However, the measurements we obtained at the nanoscale are hard to reconcile with the viscoelastic view of cell mechanical behavior. We predominantly observe elastic response with little hysteresis in the corresponding force distance curves. In addition, force distance curves are surprisingly linear, which would not be the case for viscoelastic materials indented by conical AFM tips. We have created a model for the nanomechanical response of cells that takes intracellular forces into account. The model not only explains the near-elastic response and the linearity of force distance curves, but also makes quantitative predictions about cell shape and its relationship to the local nanomechanical response. We experimentally tested and verified these predictions on cells exhibiting different morphologies. In addition to these predictions, the model allows determining intracellular forces from the AFM images, such as tension across actin fibers and cortex tension. This work expands the existing cell mechanical models into the nanoscale and enables AFM to obtain physiologically relevant parameters from mechanical images.