These tiny structures mimic the natural environment of a cell.

Biologists examine cells under a microscope on flat surfaces that look nothing like the environment inside the body. Researchers at NTNU have now found a way to mimic the environment of a cell’s natural environment by using tiny polymer pillars. The journal published their work, which was funded in part by the Research Council of Norway. Nanoscale Research Letters.

Pawel Sikorski is a professor at NTNU’s Department of Physics. He says, “Cells in the body of a human being are embedded in a complex matrix of chemicals.” This environment, known as the extracellular matrix, is a dynamic support network for cell growth. It not only provides physical scaffolding for tissues and organs but also transmits signals to aid cells in communicating with each other. Although it allows researchers to observe many cellular processes in the laboratory, it is possible to lose out by removing cells from the extracellular matrix and placing them on flat surfaces made out of glass.

Sikorski states that glass is very tough and that the cell will feel that the substrate does no deform when it pulls against it. “This induces certain types and behaviors in the cells, as well as certain processes.” They will behave differently if they are placed on something flexible and soft that can deform and be remodeled.

Researchers need a substrate that closely replicates biology if they want to understand how cells behave in the environment where they live. One option is to embed cells in hydrogels, such as 3D networks of gelatin-like proteins. However, studying cells in a hydrogel is not as simple as looking at them under an optical microscope. Sikorski says, “If you want see what’s going on it gets quite difficult.”

In a thin polymer layer, create structures

One possible solution is to mimic the mechanical properties of softer substrates by using nanostructures. That’s exactly what Sikorski (and Ph.D. student Jakob Vinje) did in collaboration with Noemi Antonella Guadagno, a cell biologist at the University of Oslo, and Cinzia PROGIDA. Vinje covered the glass slides with tiny pillars of a polymer called SU-8. These nanopillars measure just 100 nanometres across at their tip and were made using electron beam lithography (NTNU NanoLab), where a focused beam if electrons creates structures in a thin film of polymer.

Sikorski says, “Per millimeter square, you already have quite the number of pillars. If you want to study cell function, then we need to make surfaces that are at least 10 by 10 millimeters.” “The tools at NTNU NanoLab are crucial for this to be possible.”

Researchers created substrates with different nanopillar arrangements and tested them with fluorescent proteins-producing cells. The researchers examined the cells using a microscope to analyze the shape, size, and distribution of the points at the surface where the cell attaches.

Pillars that are tightly packed

The researchers made hundreds of observations of cells on different surfaces and found that substrates with tightly packed pillars closely resembled a soft surface. Sikorski states that cells behave as if they were on a harder substrate if there are dense pillars.

The beauty of nanopillar-covered substrates lies in their simplicity. In theory, biologists could swap their old glass slides for the new ones. Sikorski says, “It has more features than a glass substrate but it’s still relatively easy.”

He stated that the ultimate goal would be for researchers “to just open the package and pull out one of them, then put their cells on and then examine it under the microscope. Then throw it away when they’re done.” To make this a reality, however, the substrates must be manufactured in large quantities at a low cost.

The researchers have so far only made a few prototypes. However, there are other methods, such as nanoimprinting lithography, which could allow for scaling up production.

The substrates can be used by biologists to study cells in new ways and could also be used to improve the screening of medicines. Nanopillar-covered substrates could mimic the surface of a drug that stops cells from sticking to it.