Cancer’s Tell: Malignant Cells and “Squishiness”
Scientists are analyzing the “squishiness” of cells - a clue that can help us catch cancerous tumor growth before they become dangerous
Graphic by Ziona Somy
We might already think of our bodies as ‘squishy,’ but does a cell’s level of softness actually reveal something deeper about its function? Scientists are beginning to explore this concept, as research has discovered that while healthy cells are structured, (held together by scaffolding protein fibers giving them their shape), cancerous cells change their morphology to optimize the conditions for metastasis (spread of cancer from one region throughout the body).
Currently, we have developed a highly precise way to measure a cell’s level of squishiness, using what is called “Atomic Force Microscopy” (AFM). AFM uses a commonly known physics concept called Young’s Modulus, which calculates the ratio of tensile stress to strain to measure a given material/surface’s elasticity. To do this, AFM “pokes” a cell with a tiny needle made of silicon nitride called a cantilever (roughly the size of a human hair), and measures how much the surface pushes back. A laser beam is directed through the cantilever, and when it bends on impact, the laser shifts its reflection, which is then recorded to measure stiffness down to nanonewtons. This can be roughly comparable to the force exerted by a single bacterium (the weight of a single bacterium).
With this ability to quantify cellular elasticity so precisely, researchers began to question: what does this “squishiness” actually reveal about cancer cells? Cancer cells are often believed to be softer than healthy ones, even though this pattern is not consistent across all cancer types. For a long time, and in most cases, we have found that malignant cells become softer compared to their benign counterparts. However some conflicting evidence has shown that cells with higher motility are sometimes stiffer than their counterparts.
A research article from the Molecular Biology of the Cell Journal explores this, and finds that it might not be a consistent finding with ALL cancer types. Instead, it is a more complex process that involves the malignant cell’s interaction with their specific Extracellular Matrix (ECM). The ECM is the non-cellular complex of proteins and polysaccharides, namely collagen, that supports the cells within tissues. As you can imagine, this ECM varies depending on the tissue system being investigated. Therefore the observed morphological changes have less to do with just “getting squishy” and more to do with the cancerous cell’s interaction with the specific extracellular matrix, and adapting to allow for most efficient metastasis.
This insight creates new avenues for medicine, and cancer diagnosis. A team led by Xinyao Zhu at Tianjin University in China used this Atomic Force Microscopy combined with new trained machine learning models to be able to use AFM data to classify four grades of bladder cancer, just from their mechanical properties. This study achieved a 91.25% accuracy, which is well above what conventional cell inspection methods typically achieves, all without invasive procedure. Because stiffness is a spectrum that can help us understand and diagnose the progression of a given type of cancer, repeated measurements over time could also tell doctors how fast the tumor is growing or how effectively it is responding to treatments.
A study done at theUniversity of Illinois in 2025 helps expand even further within this field, the research has begun to see early evidence that this relationship between stiffness and malignancy can be reversed through the development of novel therapeutics targeting this process. This growing field of “mechanotherapeutics” involves the study of biological mechanisms and their physical principles, and the ways that those mechanisms can be manipulated to create modern therapeutics. In this case, exploring whether these drugs could be designed to strip malignant cells of their mechanical advantage, preventing them from reaching optimal conditions to metastasize. Therefore possibly halting the stage of cancer that makes a tumor most dangerous: the spread throughout the body.
Because metastasis is a characteristic of all late-stage cancers, contributing to an exponentially more dangerous cancer throughout the body, this research is important for us to develop tools to possibly detect these cytoskeletal changes that could indicate malignancy. This research could become a powerful tool for medicine and oncology, potentially slowing down metastasis and identifying tumor progression earlier on. Cancer, it seems, has a tell. And scientists are learning to read it.
These articles are not intended to serve as medical advice. If you have specific medical concerns, please reach out to your provider.