Abstract

Biological materials such as extracellular matrix scaffolds, cancer cells, and tissues are often assumed to respond elastically for simplicity; the viscoelastic response is quite commonly ignored. Extracellular matrix mechanics including the viscoelasticity has turned out to be a key feature of cellular behavior and the entire shape and function of healthy and diseased tissues, such as cancer. The interference of cells with their local microenvironment and the interaction among different cell types relies both on the mechanical phenotype of each involved element. However, there is still not yet clearly understood how viscoelasticity alters the functional phenotype of the tumor extracellular matrix environment. Especially the biophysical technologies are still under ongoing improvement and further development. In addition, the effect of matrix mechanics in the progression of cancer is the subject of discussion. Hence, the topic of this review is especially attractive to collect the existing endeavors to characterize the viscoelastic features of tumor extracellular matrices and to briefly highlight the present frontiers in cancer progression and escape of cancers from therapy. Finally, this review article illustrates the importance of the tumor extracellular matrix mechano-phenotype, including the phenomenon viscoelasticity in identifying, characterizing, and treating specific cancer types.

Highlights

  • The General Phenomenon of ViscoelasticityIn the nature, certain materials undergo deformations other than purely elastic ones, where the material will fully return to its original shape upon the removal of the external force

  • The viscoelasticity of the tumor extracellular matrix arises due to covalent nature of crosslinking that considers the extracellular matrix as an elastic-like network (Muiznieks and Keeley, 2013) and the strain-stiffening response of collagen scaffolds, which emerges from the network level and its connectivity (Wen and Janmey, 2013; Han et al, 2018; Jansen et al, 2018)

  • Time-dependent mechanical Atomic force microscopy (AFM) experiments utilize a quasisteady-state stress-relaxation approach, but this necessitates a fit of the force-impact curves with a predetermined phenomenological model to identify the “pseudo” material properties that delineate the viscoelastic reaction of the cells (Fischer-Cripps, 2004; Darling et al, 2007)

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Summary

Claudia Tanja Mierke *

Received: 28 September 2021 Accepted: 23 November 2021 Published: 07 December 2021 Biological materials such as extracellular matrix scaffolds, cancer cells, and tissues are often assumed to respond elastically for simplicity; the viscoelastic response is quite commonly ignored. Extracellular matrix mechanics including the viscoelasticity has turned out to be a key feature of cellular behavior and the entire shape and function of healthy and diseased tissues, such as cancer. The topic of this review is especially attractive to collect the existing endeavors to characterize the viscoelastic features of tumor extracellular matrices and to briefly highlight the present frontiers in cancer progression and escape of cancers from therapy. This review article illustrates the importance of the tumor extracellular matrix mechano-phenotype, including the phenomenon viscoelasticity in identifying, characterizing, and treating specific cancer types

The General Phenomenon of Viscoelasticity
CONCEPTS OF LINEAR AND NONLINEAR VISCOELASTICITY
Concept of Linear Viscoelasticity
Classical Concept of Nonlinear Viscoelasticity
New Concept of Nonlinear Viscoelasticity Model
APPLICATION OF THE VISCOELASTICITY ON CANCER
VISCOELASTIC PROPERTIES OF THE TUMOR EXTRACELLULAR MATRIX
Sinusoidal Testing
Network Theory
ENVIRONMENTAL MATRIX VISCOELASTICITY ACTS ON CELLS
Tumor Extracellular Matrix Environment Is Sensed by Cancer Cells
DESIGN OF HYDROGEL SCAFFOLDS THAT MIMIC TUMOR MICROENVIRONMENTS
Separation of Mechanical Characteristics From Other Matrix Parameters
Findings
FINAL REMARKS AND FUTURE PERSPECTIVES
Full Text
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