(C-107) Nanoscale viscoelastic mapping of patient primary pancreatic cancer tumors

Introduction:: Viscoelasticity is the property of a material’s viscous and elastic behavior [1-2]. Cellular functions are influenced by viscoelastic properties, as cells undergo deformation and relaxation in response to mechanical forces, both internal and external. Additionally, tissue viscoelasticity is crucial for biological functions such as tissue development and response to mechanical trauma or stress. Biomedical imaging procedures, such as ultrasound, X-ray, and elastography, can reveal important details about tissue properties and diagnose diseases in vivo, however these techniques provide images with low spatial resolution and are unable to provide quantitative material properties measurements. Atomic force microscopy (AFM) is an effective and flexible instrument for analyzing mechanical properties in various contexts [3], including cancer tissues. Cancer tissues’ tendency to exhibit altered mechanical properties due to microenvironmental and cellular alterations makes AFM-based elasticity studies practical in terms of discriminating between normal and malignant tissues.

In this study, we used a viscoelastic model to characterize and compare the material behavior of normal adjacent tissue and pancreatic cancer tissue taken from the same patient. Pancreatic cancer is currently one of the most lethal malignancies worldwide, principally due to difficulty with early detection and poor response rates to conventional chemotherapeutics. Since pancreatic cancer is highly desmoplastic, we hypothesize that the cancer tissue’s ECM fibers will exhibit greater amounts of viscoelastic response compared to the normal adjacent tissue.

Materials and Methods:: We took samples of patient-derived normal adjacent and cancer tissue and compared their mechanical and structural properties. The samples were embedded in 8% agarose and were sliced using a vibratome. Then they were examined using AFM at physiologically relevant conditions. Data collected from these AFM studies were analyzed using a viscoelastic model, yielding high resolution maps detailing the topography, storage moduli and loss moduli of the tissue samples. A map of the loss angle was generated using the tangent of the loss moduli and the storage moduli.

Results, Conclusions, and Discussions::
Our preliminary results show significant changes in the elastic storage and viscous loss modulus of primary cancer tissue compared to normal tissue associated with the tissue’s ECM fibers. The loss angle in the normal tissue was observed to be greater than that of the cancer tissue, suggesting that the cancer tissue’s material behavior is mainly dominated by changes in stiffness than viscosity when compared to the normal tissue. Additionally, collagen IV was observed by immunofluorescence and shown to be more abundant and linear in cancer tissue, further supporting the AFM results.

These findings indicate drastic mechanical and structural differences between normal and cancer tissues that are observable through AFM-based studies. Future studies will examine the viscoelastic model’s utilization as a means to extract more mechanical and structural data from cellular processes and how this data can be used to differentiate between normal and cancerous tissues, as well as exploring the mechanical and structural differences at metastatic lesions.


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[1] Chaudhuri, O. et al. Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature 584, (2020)

[2] Solares, S.* & Cartagena-Rivera. A. X. Frequency-dependent nanomechanical profiling for medical diagnosis. Beilstein J. Nanotechnol. 13, 1483-1489 (2022)

[3] Parvini, C. H., Cartagena-Rivera, A. X. & Solares, S. Viscoelastic parametrization of human skin cells characterize material behavior at multiple timescales. Commun. Biol. 5, (2022)