Probing Viscoelastic Properties of Biomolecular Condensates with Passive Micro-Rheology

Multicomponent nanomaterials with the ability to create extensive crosslinking typically exhibit a complex interplay of viscous and elastic properties. We have utilized particle tracking (PT) microrheology to characterize nucleic acid-based nanomaterials cross-linked with Quantum Dots (QDs) which maintain a substantial contribution of liquid phase still diffusing through the system. The physical properties of such condensates were investigated thoroughly using PT microrheology which analyzes the motion of polystyrene beads inserted into the condensates. The setup requires thorough calibration which was achieved using a set of glycerol/water mixtures of known viscosity values. We analyzed motion of beads using the average mean-squared displacement as a function of lag time which yielded two parameters: Diffusion coefficient and the power of the lag time. The diffusion coefficient is inversely proportional to viscosity reporting on the rate at which beads diffuse within the condensates. The lag time power identifies the viscoelastic state of the material. Our measurements show that by varying the length of DNA crosslinks (27, 39, 66 base pairs long) it is possible to tune viscoelactic properties of the condensates. The microstructure of these materials could be made responsive to external triggers such as presence of DNase or Ethidium Bromide. DNA removes crosslinks while EtBr results in condensate swelling changing the microstructure and, in turn, viscoelastic response of the materials.