The mechanical memory of cells

Bioengineering Professor Joseph Irudayaraj and his team were applying force to cell surfaces to study the effect on the diffusion of protein molecules in the nucleus when they observed something unexpected: the cell nuclei in the experiment could remember the force that had been used on them earlier.

“We never expected to see that,” said Irudayaraj. “But when we analyzed the data, we found that the proteins were diffusing more rapidly because they remembered the forces that had elevated the diffusion previously. It’s like having somebody pinch you; you feel the pain for a moment even after the pinch is gone.”

This fascinating research was the result of a collaboration with Mechanical Science and Engineering Professor Ning Wang, an expert in cell mechanobiology. PhD students Wenjie Liu from Bioengineering and Fazlur Rashid from MechSE initiated the collaboration. The team recently published their findings in the journal Proceedings of the National Academy of Sciences (PNAS), titled “Mechanomemory in protein diffusivity of chromatin and nucleoplasm after force cessation.”

Until now, very little was known about the mechanical memory of cells as it relates to the diffusion of protein molecules in the cell nucleus, which makes these findings particularly groundbreaking.

“The additional experimental results in live cells show that the protein diffusion in the nucleus and thus the nuclear mechanomemory are regulated by the size and the number of the pores at the nucleus membrane that control the exchanges of molecules between the nucleus and the cytoplasm,” said Professor Wang.

After examining the results of a molecular dynamics simulation, the team also found that reducing the local density of protein molecules as a result of the tensile strain on the chromatin network in the nucleus contributed to the duration of the nuclei’s memory.

In addition to filling a cellular knowledge gap, this research could serve as a knowledge baseline in understanding the effect of forces on proteins that participate in gene regulation. Understanding how these microscopic proteins move in different environments in the cell nucleus, particularly within either dense or loosely packed chromatin within a cell, could provide insights on treating stiff muscles, disease progression, and even cancerous tissues.

While there are broad-reaching health implications in the future, particularly with respect to therapy, Irudayaraj emphasized that for now they’re focused on understanding what is happening at a cellular level.

“What we are studying is at the intersection of biophysics and mechanobiology at the single cell level,” said Irudayaraj. “It's a very, very basic question that we are asking at this point.”

Irudayaraj credited the success of this research to his highly collaborative team, as well as the computational work that validated their most recent experimental findings and discovered the underlying mechanism.