Cell Nuclear Force Probe Reveals Mechanomemory That May Impact Cell Memory and Health
BioE Professor Ning Wang published research in Cell Reports that demonstrates a process of mechanomemory, or response long after applied force has ceased, within a cell’s nucleus. This discovery prompts a prolonged period of activation of a protein complex responsible for gene expression, which can lead to making new proteins and potentially healthier cells.
Main photo: Ning Wang (left) with co-authors Fazlur Rashid and Sadia Kabbo, who are PhD students.
Ning Wang, professor of bioengineering and director of the Institute for Mechanobiology, co-authored a paper with two PhD bioengineering students he advises, that was published in Cell Reports and details their research on creating mechanomemory within the nucleus of a cell, which could lead to biological changes that would impact the cell’s overall memory and health.
The paper, “Mechanomemory of Nucleoplasm and RNA Polymerase II After Chromatin Stretching by a Microinjected Magnetic Nanoparticle Force,” presents their data showing how a cell’s nucleus can be injected with a magnetic nanoparticle force probe directly into the nucleus that houses DNA and proteins of a hamster epithelial cell or a human stem cell. Application of the nanoparticle force for only a few minutes causes elevated diffusive movements of the chromatin and the nucleoplasm within the nucleus. However, once the applied force has been removed, these structures and the protein complex of RNA polymerase II in the nucleus continue their elevated diffusive movements for many minutes.
Wang’s team applied a magnetic field around a cell after they injected the cell with a magnetic nanoparticle that attaches specifically to a histone protein (H2B) on the chromatin. When the team oscillated the magnetic field, the nanoparticle oscillated at the same rate as well. This, in turn, triggered oscillatory stretching of the chromatin. However, after the magnetic field was terminated, there were prolonged periods of elevated diffusive movements of the chromatin and the nucleoplasm, and of RNA polymerase II activity, prompting prolonged duration of gene expression.
The size of the nanoparticle, 200-nanometer, about 2/1000th of a human hair, was critical as a direct chromatin force probe and to the successful outcome of the research, Wang notes. A much larger particle would have caused damage or substantial perturbations to the nucleus and too small a nanoparticle would only probe the liquid part of the nucleus. Using this nanoparticle force probe, the team found that the chromatin or the nucleoplasm in the nucleus behaves as a viscoelastic gel-like structure, not as a liquid, as earlier studies suggested.
Wang and his research team, including co-authors Fazlur Rashid and Sadia Kabbo, plan to extend their work to understand how to repair human aging tissue or keep it healthy for longer periods of time, which, if extended to the organ and whole-body levels, could have a significant impact on older individuals.
“This is very important because as the population get older and older, we have to find more ways to keep people healthy,” Wang says.