Nano-jab reveals cell responses

By giving living cells a “nano-poke” and monitoring the resulting changes in the intracellular environment, researchers have gotten their first glimpse of how whole cells respond to external mechanical pressure.

A team led by scientists from the National Institute for Materials Science (NIMS) in Tsukuba, Japan, used a technique called atomic force microscopy to apply force across the surface of various cells. The method uses nanoscale probes, with tips just a few billionths of a metre in size, to measure and map how force gets distributed across the cellular surface and throughout the cell. The researchers used machine learning to analyse and model the forces they measured. They also used fixing and staining techniques to study how the force distortion affected the cell’s internal structures and the microtubules and actin filaments that make up its “skeleton”. The study was published in the journal Science and Technology of Advanced Materials.

“Cells are smart materials that can adapt to various chemical and mechanical stimuli from their surroundings,” says Jun Nakanishi, one of the corresponding authors of the study and the leader of the Mechanobiology Group at NIMS. That ability to adapt relies on rapid feedback mechanisms to keep the cell intact and healthy, and there’s growing evidence that the failure of this cellular response underlies a range of ailments, including diabetes, Parkinson’s disease, heart attacks, and cancer.

So far, studies of these cellular responses have been limited by the techniques used – for example, some methods require that cells be pre-fitted with sensors, so they can only measure a small part of the response. “We invented a unique way to ‘touch’ a cell with nanoscale ‘hand’, so that the force distribution over a complete cell could be mapped with nanometre resolution,” says Hongxin Wang, who is the first author of the study and Japan Society for the Promotion of Science (JSPS) postdoc in the Mechanobiology Group.