During the last decade, the development of nanomaterials to penetrate inside living cells has been the focus of a large number of studies, with applications for the biomedical field. However, the further dynamics of these nanomaterials inside the cells is dictated by the intracellular environment and in particular its mechanical properties. The mechanical characteristics of the cell interior can be probed with either active or passive microrheological approaches. However, active intracellular microrheology is still in its infancy, owing to the difficulty of inserting probes that can be manipulated by external forces. Here we review recent active microrheology studies using magnetic nanoprobes inserted into endosomes or phagosomes as useful approaches for measuring frequency-dependent viscoelasticity, for mapping the viscoelastic landscape, as well as for identifying the contribution of individual cytoskeleton components and the influence of cell motility. The results of such direct measurements challenge the validity of more typical passive approaches in which the spontaneous displacement of embedded nanoprobes is measured. Here we discuss that one must distinguish probes suitable for use in conditions of thermal equilibrium, whose movements reflect the mechanical environment from probes that interact actively with the cytoplasm and cytoskeleton, in a state of nonequilibrium for which fluctuation-dissipation theorem no longer holds. However, when data on these probes’ viscoelastic microenvironment is available, such passive probe movements can yield useful information on the forces responsible for intracellular activity.

• Received 21 September 2011

DOI:https://doi.org/10.1103/PhysRevE.85.011905