Nanoscale probes reveal how cell structure responds to pressure

By giving living cells a ‘poke’ and monitoring the resulting changes in the intracellular environment, scientists at Japan’s National Institute for Materials Science (NIMS) have gotten their first glimpse of how whole cells respond to external mechanical pressure, with their results published in the journal Science and Technology of Advanced Materials.

The scientists used atomic force microscopy to apply force across the surface of various cells; the method used 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, while fixing and staining techniques were used to study how the force distortion affected the cell’s internal structures and the microtubules and actin filaments that make up its ‘skeleton’.

“Cells are smart materials that can adapt to various chemical and mechanical stimuli from their surroundings,” said co-corresponding author Jun Nakanishi. 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. As explained by first author Hongxin Wang, “We invented a unique way to ‘touch’ a cell with a nanoscale ‘hand’, so that the force distribution over a complete cell could be mapped with nanometre resolution.”

The study revealed that tensional and compressional forces are distributed across actin fibres and microtubules within the cell to keep its shape, similar to how the poles and ropes of a camping tent work. When the researchers disabled the force-bearing function of actin fibres, they found that the nucleus itself is also involved in counterbalancing external forces, highlighting the role of the internal structure of the nucleus in the cellular stress response.

The research team also compared the responses of healthy and cancerous cells. Cancer cells proved more resilient to external compression than the healthy cells, and they were less likely to activate cell death in response.

Not only do the findings illuminate the complex intracellular mechanics of the stress response, but the discovery of different responses in cancer cells could offer a new way to distinguish healthy and cancerous cells — a diagnostic tool based on cellular mechanics. Hospitals currently use the size, shape and structure of a cell in diagnosing cancer, but these features don’t always provide enough information to tell the difference between healthy and diseased cells.

“Our findings provide another way of checking cell conditions by measuring force distribution, which could dramatically improve diagnostic accuracy,” said co-corresponding author Han Zhang.

Image credit: iStock.com/Sebastian Kaulitzki