PoC - Physics of Cancer - Annual Symposium
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Contributed Talk, Saturday, 10:15 – 10:30  
How changes in cell mechanical properties induce cancerous behavior

Parag Katira1, Muhammad H. Zaman2, Roger T. Bonnecaze1
 
1
 The University of Texas at Austin, Austin, TX, USA
2
 Boston University, Boston, MA, USA

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Numerous experiments have shown the differences between the mechanical properties of healthy and cancerous cells – particularly in terms of cell compliance and inter-cellular adhesivity. While it has been suggested that these mechanical property changes play a significant role in the progression of cancer hallmarked by uncontrolled cell division and migration resulting in tumor growth and metastasis, the exact mechanism behind this is unclear. Furthermore, the prime focus of understanding the origin of cancer as well as potential treatment options has been on determining the role of various biochemical factors. The success of this approach is greatly hindered by the heterogeneity of these factors not only across different cancers but also across different phenotypes of the same cancer as well as the strong inter-dependence of these biochemical factors on each other.
We hypothesize that cancerous behavior of cells is primarily a physical process driven by changes in cell mechanical properties that provide the forces required for cell growth, division and migration. The biochemical factors play mainly an indirect role by causing these mechanical property changes in cells. Based on this hypothesis, we have developed a computational model that describes the physical interaction of cells comprising a 3D homeostatic tissue and show how changes in the mechanical properties of a few cells within this tissue can induce uncontrolled division and cancerous behavior of these cells. The model focuses on an active role of cell mechanical property changes that influence cellular stretch and cell death or division probability is based on the resulting cell area as shown experimentally by Chen et al., Geometric control of cell life and death, Science (1997).
Simulations based on this model show that an increase in the elastic compliance of a few cells can cause them to undergo uncontrolled division and evade cell death, representing cancerous behavior. It is also observed that for these mutated cells to grow into malignant tumors there exists a minimum starting number of initial mutated cells clumped together within the tissue. The simulations also show that an increase in inter-cellular adhesion amongst mutant cells results in rapidly growing compact malignant tumors while a decrease in the mutant cell adhesivity results in more spread-out, finger-like, stunted tumors (Fig. 1). These observations can be qualitatively compared to a number of experimental and clinical observations.
The model provides a common mechanistic pathway linking the various biochemical factors that cause cell mechanical property changes to cancer progression as well as opens up novel avenues for cancer treatment focused on manipulating the cellular mechanical properties such as compliance and adhesivity.

Fig.1: Effect of changes in cell compliance and adhesivity on tumor growth and morphology. Right panel shows tumor morphology after 14 simulation cycles. The tumor cells are embedded within a homeostatic tissue and surrounded by healthy cells (not shown).
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