Abstract
Viscoelasticity and its alteration in time and space has turned out to act as a key element in fundamental biological processes in living systems, such as morphogenesis and motility. Based on experimental and theoretical findings it can be proposed that viscoelasticity of cells, spheroids and tissues seems to be a collective characteristic that demands macromolecular, intracellular component and intercellular interactions. A major challenge is to couple the alterations in the macroscopic structural or material characteristics of cells, spheroids and tissues, such as cell and tissue phase transitions, to the microscopic interferences of their elements. Therefore, the biophysical technologies need to be improved, advanced and connected to classical biological assays. In this review, the viscoelastic nature of cytoskeletal, extracellular and cellular networks is presented and discussed. Viscoelasticity is conceptualized as a major contributor to cell migration and invasion and it is discussed whether it can serve as a biomarker for the cells’ migratory capacity in several biological contexts. It can be hypothesized that the statistical mechanics of intra- and extracellular networks may be applied in the future as a powerful tool to explore quantitatively the biomechanical foundation of viscoelasticity over a broad range of time and length scales. Finally, the importance of the cellular viscoelasticity is illustrated in identifying and characterizing multiple disorders, such as cancer, tissue injuries, acute or chronic inflammations or fibrotic diseases.
Highlights
TO THE PHENOMENON OF VISCOELASTICITY IN CELLSThe phenomenon of viscoelasticity can be found in nature in several kinds of material, such as in the most prominent example, rubber, and can be employed in engineering of synthetic or biological materials
The results indicate that label-free Quantitative phase rheology (QPR) can be utilized to evaluate cell stiffness and viscosity, which confers an advantage over conventional biophysical techniques for examining the mechanical characteristics of cells and greatly broadens the use of Quantitative phase imaging (QPI) to monitor cell performance (Table 1)
While this simple linear two-parameter model is a somewhat streamlined perspective on cell viscoelasticity, this model still accurately grasps the key attributes that have been delineated in the data. This physical explanation of the mathematical model contains an inertia expression, it still reflects the response of a fluid exhibiting a low Reynolds number. This phenomenological hypothesis permits fitting a two-parameter viscoelastic model and deducing the rheological features of the cells based on the QPI data, which correspond to the atomic force microscopy (AFM) results
Summary
The phenomenon of viscoelasticity can be found in nature in several kinds of material, such as in the most prominent example, rubber, and can be employed in engineering of synthetic or biological materials. For solids, pure strains can affect the reaction of the material, while rotations can have no effect (Truesdell et al, 2004) When addressing viscoelasticity, it has to be taken into account that the inelastic response is present (Trepat et al, 2007), even though the response may not really be permanent or irreversible and can be reversible plastic (Gralka and Kroy, 2015). Viscoelastic characteristics of cells have been proposed to play a key role in the regulation of cellular functions, such as motility (Barriga and Mayor, 2019; Burla et al, 2019; Petridou and Heisenberg, 2019; Chaudhuri et al, 2020). The review pursues a hierarchical structure that reflects the spatial scale, ranging from firstly molecular mechanosensing between cells and cell matrix, to secondly transcriptional regulation leading to thirdly changes in cell state, such as epithelial to mesenchymal transition (EMT), encompassing single cell migration, to fourthly multicellular processes, including collective migration, spheroid and tumeroid biology, and fifthly disease states such as cancer, fibrosis, and others
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