Studying the viscoelasticity of cells without external rigid probes

Microrheology is a technique that measures viscoelastic properties, often used to identify changes inside a cell related to stress or disease. Typical microrheology methods track the motion of small rigid particles inserted into cells. However, introducing these external probes can disturb the system, making it unclear what originally caused the viscoelastic changes.

Brzezinski et al. introduced soft probe particle tracking microrheology (S-PTM), which tracks the motion of membraneless organelles or other subcompartments within cells to measure mechanical properties of the surrounding environment without a foreign probe.

“This turns the old idea of particle tracking into something simpler and more robust, because the cell supplies the probes and the locations for us,” said author Sapun Parekh. “We did not reinvent the wheel, but we found a way to ride the wheel already in the cell.”

The authors applied S-PTM to the nucleolus, a membraneless organelle responsible for ribosome synthesis in cells. The measurements showed that while both assessed layers of the nucleolus behave like viscoelastic solids, one of the layers is more solid-like, demonstrating that this method can resolve the distinct properties of the different nucleolar parts.

S-PTM could be applied to other membraneless organelles and various biological or synthetic systems. For example, this method could be used to evaluate drug- or gene-induced changes in disease model cells.

“Our approach allows anyone with a confocal microscope to measure mechanics,” said author Mateusz Brzezinski. “That makes biophysical measurements more accessible to cell biologists, not just rheology experts.”

Next, the authors plan to automate aspects of the method and apply it to other organelles and cell states.

Source: “Soft probe particle tracking microrheology using membraneless organelles to study viscoelasticity of nucleolar subcompartments,” by Mateusz Brzezinski, Pablo G. Argudo, Yuki Hayashi, Jasper J. Michels, Sara Cuylen-Haering, and Sapun H. Parekh, Biointerphases (2025). The article can be accessed at https://doi.org/10.1116/6.0004906 .