• A Comparison of the Biomechanical Characteristics of Cancer Cells and the Effect of Scaffold Mechanical Conditions on the Cellular Behavior
  • Elnaz Abedini,1,*
    1. doctoral student in Biomedical Engineering, PhD Program, Department of Biomedical Engineering, karabuk ,Turkiye


  • Introduction: Cancer is one of the most frequent pathologies causing death in all parts of the globe, and its pathophysiology is associated with not only genetic and molecular changes but also with considerable biomechanical changes at cellular and tissue levels. Cancer cells have a significant impact on the mechanical properties of the microenvironment around them on tumor progression, metastasis, and resistance to therapy. The study of the biomechanical properties of malignant cells has become a key part of cancer biology with potential insights to cellular behaviors that are complementary to current standard approaches based on the molecular perspective of cancer. Mechanotransduction pathways are key to how the tumor microenvironment, specifically the mechanical properties of the extracellular matrix scaffolds, affects the behaviors of the cancer cells. Recent improvements in the techniques of biomechanical characterization and scaffold engineering have offered unprecedented possibilities of studying the role of mechanical cues in the regulation of cancer cell proliferation, migration, invasion and sensitivity to pharmaceuticals. The objective of the review is to review all the existing knowledge and information on the biomechanical properties of cancer cells in detail, as well as assess the impact of the mechanical environment of scaffolds on the behavior of malignant cells, thus, facilitating the creation of more effective therapeutic and diagnostic methods.
  • Methods: The systematic review was performed based on the peer-reviewed publications that included biomechanical studies of cancer cells and scaffold-based studies published between 2015 and 2024. Various databases such as PubMed, Web of Science, and Scopus were searched by using specific keywords that pertained to cancer biomechanics, mechanobiology, scaffold stiffness and mechanotransduction. Search terms included: cancer cell mechanics, tumor stiffness, mechano-transduction pathways, scaffold mechanical properties and extracellular matrix stiffness. The studies were chosen according to their relevance to cancer cell bio-mechanical characterization, mechanical signaling through scaffolds, and mechanobiological studies in cancer biology. The types of experimental techniques reviewed were atomic force microscopy, which is used to measure mechanical forces exerted on individual cells, micropipette aspiration, optical tweezers, which is used to measure cell force, traction force microscopy, and various scaffold fabrication technologies such as hydrogels, electrospun fibers and 3D bioprinting technologies. In vitro cell culture experiments involving substrates of differing mechanical properties, in vivo tumor mechanics experiments and computational modeling strategies to understand the mechanobiological phenomena of cancer progression are also included in the review.
  • Results: It can be seen that cancer cells have dramatically different biomechanical characteristics than their healthy counterparts, and that malignant cells usually show decreased stiffness, increased deformability, and increased migratory ability. Measurements of those quantities indicate that cancer cells have a Youngs modulus between 0.1 and 2 kPa, which is significantly lower than normal cells with stiffness values of between 2-10 kPa. Such mechanical changes are associated with a high probability of metastasis and invasion. Scaffold mechanical properties have a significant impact on cancer cell behavior, and substrate stiffness is an important regulator of cellular functions. Investigations indicate that soft scaffolds (0.1-1 kPa) can be used to induce cancer cell stemness and drug resistance, whereas intermediate stiffness levels (1-10 kPa) can be used to induce proliferation and migration. In some cancer types, rigid scaffolds (>10 kPa) tend to cause apoptosis or growth arrest. The response of cells to mechanical stimuli is mediated by such signaling pathways as mechanotransduction through integrins, focal adhesion kinase, and Yes-associated protein signaling. Three-dimensional Scaffold structures expose intricate connections between mechanical features and topographical stimuli, which affect invasion phenotypes of cancer cells and therapeutic outcomes. Review reveals that the determinants of cancer cell fate decisions are the important mechanobiological factors (substrate elasticity, viscoelasticity, porosity, and roughness of the surface).
  • Conclusion: Results emphasize the inherent role of biomechanical factors in cancer biology and how these factors may be utilized therapeutically. The mechanical differences between normal and malignant cells we observed indicate that biomechanical characteristics may be used as diagnostic biomarkers to identify cancer and monitor its progression. The effects of scaffold mechanical environments on cancer cell behavior offer a useful example of how to create biomimetic models that better replicate tumor micro-environment to be used in drug screening and to develop therapeutic agents. The defined mechanotransduction pathways are potential therapeutic targets in interfering with cancer cell adaptation to mechanical stimuli. Nevertheless, mechanical signaling networks and their interactions with biochemical factors are challenging to translate to clinical applications. Future research priorities should be set on standardized mechanical characterization regimens, evidence of mechanobiological heterogeneity across populations of tumors, and personalized mechanical interventions based on personal tumor mechanical signatures. Biomechanical applications combined with classical molecular treatments is another promising direction of enhancing the efficacy of cancer treatment and addressing mechanisms of therapeutic resistance.
  • Keywords: biomechanics, cancer cells, scaffold stiffness, mechanotransduction, tumor microenvironment.