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Mechanical properties of human tumour tissues and their implications for cancer development

Abstract

The mechanical properties of cells and tissues help determine their architecture, composition and function. Alterations to these properties are associated with many diseases, including cancer. Tensional, compressive, adhesive, elastic and viscous properties of individual cells and multicellular tissues are mostly regulated by reorganization of the actomyosin and microtubule cytoskeletons and extracellular glycocalyx, which in turn drive many pathophysiological processes, including cancer progression. This Review provides an in-depth collection of quantitative data on diverse mechanical properties of living human cancer cells and tissues. Additionally, the implications of mechanical property changes for cancer development are discussed. An increased knowledge of the mechanical properties of the tumour microenvironment, as collected using biomechanical approaches capable of multi-timescale and multiparametric analyses, will provide a better understanding of the complex mechanical determinants of cancer organization and progression. This information can lead to a further understanding of resistance mechanisms to chemotherapies and immunotherapies and the metastatic cascade.

Key points

  • Changes in molecular-level, cellular-level and tissue-level mechanical properties across multiple timescales and dimensions play a critical role in driving oncogenesis, tumour organization and disease progression.

  • An array of cellular and tissue mechanical properties, including surface tension, hydrostatic pressure, elasticity, viscosity and adhesion, can provide greater insights into distinguishing unique characteristics of different cancers.

  • Comprehensive supplementary tables gathering quantitative mechanical properties values of human cancer cells and tissues provide details of cancer development from a biomechanical perspective.

  • Quantification of multiple physical parameters of cells and tissues provides a multiscale, multidimensional and multiparametric understanding of physical oncology for the development of prognostic and diagnostic tools.

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Fig. 1: Remodelling of the cellular cytoskeleton and extracellular matrix is a hallmark of cancer-causing alterations in cellular mechanical properties.
Fig. 2: Mechanobiological techniques used to quantify multiple mechanical properties at both the cellular and tissue levels.
Fig. 3: Diverse changes in intratumoural microenvironmental architecture and mechanical properties for different cancers.

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Acknowledgements

The authors acknowledge the help of A. Hoofring (Medical Arts Design Section, NIH) with preparation of the figures. The authors thank M. Mezher and A. Bluem for critical reading and thoughtful comments. The authors sincerely apologize to the many researchers whose relevant work we were unable to cite owing to space limitations. The authors acknowledge support by the intramural funding of the Division of Intramural Research Program at the National Institute of Biomedical Imaging and Bioengineering with grant ZIA-EB000094 and the NIH central funds for the NIH Distinguished Scholars Program award.

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Glossary

Actomyosin

Contractile filamentous actin network inside the cell that helps provide shape, motility and force generation for a cell. The actomyosin cytoskeleton consists of filamentous actin, non-muscle myosin II motor proteins and regulatory actin-binding proteins.

Adhesion force

In biological terms, adhesion occurs directly between neighbouring cells via specialized proteins on the cell surface and indirectly via the extracellular matrix, both of which allow cells to communicate with one another and respond to their environment through processes such as signal transduction. In physics terms, adhesion is a type of attractive force that occurs between different objects through mechanical forces and electrostatic interactions.

Cellular tension

The surface force needed to stretch the cell, which is dependent on its plasma membrane lipid composition, extracellular glycocalyx and the contractile forces of the intracellular actin cytoskeleton, all of which must be overcome to deform the cell.

Cytoskeletons

Complex skeletal networks of proteins that provide structure to cells and play a major role in organization, motility and mechanotransduction. Several major components of this system include actin filaments, microtubules and intermediate filaments, which may be the stiffest structures in a cell.

Glycocalyx

An extra-membranous coating rich with glycans and various transmembrane proteins, which typically act as a barrier against the environment.

Intracellular forces

The different types of physical forces that exist within cells to maintain cellular homeostasis and cell-specific normal function. The major forces acting within a cell are tensional and compressive forces acting at the surface and cytoskeleton and traction forces at focal adhesions.

Mechanosensation

The ability of a cell to sense and respond to mechanical stimuli in its microenvironment, including different types of stresses, strains and forces.

Morphogenesis

The biological process that includes the development of cells, tissues or organs into a specified shape. This process is fundamental for developmental biology and tissue growth, both regulated and unregulated. Morphogenesis is also responsible for cellular differentiation.

Tumour microenvironment

A complex, highly heterogeneous space consisting of a mixture of cancer cells, extracellular matrix, cancer-associated fibroblasts, immune cells and lymphatic vessels.

Viscoelasticity

The mechanical behaviour of most soft ‘squishy’ materials exhibits both storage of elastic energy (solid behaviour) and dissipation of mechanical energy (fluid behaviour) when undergoing deformation. Viscoelasticity is a measurable retarded tendency of a material to return to its original shape after an applied force is removed.

Viscosity

The resistance of a liquid to flow, the deformation of which is dependent on energy being dissipated or lost by its internal friction, or force per unit area and time (Pa s). More viscous liquids have a higher internal friction.

Young’s modulus

A measure of tensile elasticity that indicates how much a material can deform for an applied force. It is defined as the ratio between stress, the force per unit area, and strain, extension per unit length (dimensionless). For soft materials such as living cells and tissues, it is applicable before the elastic region limit in which linearity breaks down and plastic deformation occurs. The higher the value is for Young’s modulus, the stiffer the material.

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Massey, A., Stewart, J., Smith, C. et al. Mechanical properties of human tumour tissues and their implications for cancer development. Nat Rev Phys 6, 269–282 (2024). https://doi.org/10.1038/s42254-024-00707-2

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