"We are now able to see these features because our approach allows us to take measurements within living, intact, 3D tissues," says Chris Moraes, from McGill University's Department of Chemical Engineering, a Canada Research Chair and senior author on a recent research paper in Nature Communications. "When tissue samples are disrupted in any way, as is normally required with standard techniques, signs of these 'hot spots' are eliminated."

"Smart" hydrogels provide information about cancer progression

The researchers built tiny hydrogel sensors that can expand on demand, much like inflating balloons the size of individual cells, and placed them inside 3D cultures and mouse models of breast cancer. When triggered, the expansion of the hydrogel can be used to measure very local stiffness inside the tumour.

This unusual technique, developed through a collaboration between McGill's Department of Chemical Engineering and the Rosalind and Morris Goodman Cancer Research Centre at McGill, allows the researchers to sense, from the perspective of a cancer cell, what is going on in their surrounding environment.

What cells sense drives their behaviour

"Human cells are not static. They grab and pull on the tissue around them, checking out how rigid or soft their surroundings are. What cells feel around them typically drives their behaviour: immune cells can activate, stem cells can become specialized, and cancer cells can become dangerously aggressive," explains Moraes. "Breast cancer cells usually feel surroundings that are quite soft. However, we found that cancer cells inside aggressive tumours experienced much harder surroundings than previously expected, as hard as really old and dried up gummy bears."

The researchers believe that their findings suggest new ways in which cell mechanics, even at the early stages of breast cancer, might affect disease progression.

"Developing methods to analyze the mechanical profiles in 3D tissues may better predict patient risk and outcome," says Stephanie Mok, the first author on the paper and a PhD candidate in the Department of Chemical Engineering. "Whether these 'hot spots' of stiffness are really causing cancer progression rather than simply being correlated with it remains an open, but critically important question to resolve."

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Materials provided by McGill University. Note: Content may be edited for style and length.

Journal Reference:

1. Stephanie Mok, Sara Al Habyan, Charles Ledoux, Wontae Lee, Katherine N. MacDonald, Luke McCaffrey, Christopher Moraes. Mapping cellular-scale internal mechanics in 3D tissues with thermally responsive hydrogel probes. Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-18469-7