Nat. Commun. 10, 1652 (2019)

Cell function results from the interplay between the nanoscale organization of macromolecules and their dynamic behaviour. Yet understanding how they are linked has proven challenging due to the limitations of current microscopy techniques, which can only probe a few molecules at a time and which require the addition of an exogenous — often cytotoxic — dye, frequently leading to heterogeneous labelling and photobleaching.

In their recent paper, Gladstein and co-authors present a label-free optical technique named dual partial wave spectroscopy (dual-PWS), which measures the spectral and temporal variation of the interference signal of light back-scattered from macromolecular assemblies within a cellular sample. The technique provides information on the spatial organization and motion of intracellular macromolecular structures at a single-cell level, with nanoscale and millisecond resolution. For example, it confirms the high mobility and structural heterogeneity of chromatin in stem cells, which enables access to several genes for cell differentiation. Using dual-PWS the authors also show that, in cells exposed to UV radiation, the intracellular macromolecule ensemble experiences a previously unnoticed burst of activity — dubbed cell paroxysm — connected to cytoskeleton and cell membrane damage, which they suggest might be related to the early phases of cell death.