Could stretching cells be the way to diagnose cancer? Claudia Brunner at the University of Leipzig, Germany, takes a biomechanical approach to medicine ¹

The 1991 Nobel laureate in physics Pierre-Gilles de Gennes stressed that the importance of results in biological physics can be measured by their medical impact, since any important biological finding must also influence medicine. Studies of cellular biomechanics are on the verge of fulfilling de Gennes' ambitious demand. 

Over the past 20 years techniques to measure cell biomechanics have improved tremendously. So too has theoretical insight into the behaviour of worm-like biopolymers such as are found in the cell cytoskeleton - the mixture of microtubules and filaments that provide scaffolding for the cell. The result is that distinguishing cells by their functional biomechanical properties has become a valuable cell marker. 

For example, it is now possible to use biomechanical studies to investigate such important phenomena as cancer. During the cancerous descent of a cell its cytoskeleton regresses from an ordered and fairly stiff structure to a more irregular and compliant state. Phenotyping individual cells according to their mechanical properties is a novel approach to identifying cancerous cells by correlating these cytoskeletal changes with malignancy. 

Devices such as the optical stretcher (top) or techniques such as scanning force microscopy (bottom) can be used to measure cells' biomechanical properties

However, there is no benefit in only recognising a cancer cell by its biomechanical properties. Imaging techniques are so refined that even small-sized tumours can be easily recognised and conventional pathology of these tumours can safely diagnose cancer. Biomechanical measurements have to provide information that cannot be delivered by normal diagnosis. Here, the two main requirements for state-of-the-art cancer diagnosis are earlier detection that can be used in cancer screening, and a refined staging of tumour progression. In both cases biomechanical measurements show great promise.

The optical stretcher is one tool for quantifying biomechanical properties such as cell elasticity. The system takes measurements from a single cell by using a pair of laser beams to manipulate and stretch the cell in a microfluidic setup. Recently the device has been used to diagnose dysplasia (a pre-cancerous change in cells and tissues) in the mouth.² This could one day lead to screens for oral cancer at routine dental check-ups; cells could be extracted from the lining of the mouth with specially designed brushes (cytobrushes) and then analysed. 

Biomechanical measuring systems, such as the optical stretcher or scanning force microscopes, also have the potential to be used in breast cancer diagnosis. Conventional pathology of breast tumours provides no conclusive information about metastasis - the cancer's spread. Instead, the sentinel lymph node - the lymph node closest to the tumour - is typically removed during breast cancer surgery to look for signs of breakaway cells. By detecting metastatic cells directly in the primary tumour, biomechanical measuring systems may avoid the need to remove the lymph node. 

Cancer cells' ability to migrate shows how important it is to have a deeper understanding of cell motility and how this movement is generated. That means, besides investigating changes in passive biomechanical properties, the integration of active biomechanics is needed. A quantitative comprehension of how cells move may lead to new strategies in reducing metastasis by inhibiting cancer cell motion.

Isolating cells according to their biomechanical signature has the potential to be a key technique in emerging scientific fields. This novel approach to precisely distinguish different cell types has promise for cancer diagnostics, as well as for isolating rare cells such as stem cells more accurately. The growing success found in using a cell's biomechanical properties as a marker illustrates how novel insights into the physics of semiflexible polymers can lead to important applications in biomedicine and biotechnology.

Read more in the review 'Passive and active single-cell biomechanics: a new perspective in cancer diagnosis' in Soft Matter.

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