Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction

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.

Developing Bovine Brain-Derived Extracellular Matrix Hydrogels: a Screen of Decellularization Methods for Their Impact on Biochemical and Mechanical Properties

“…Although there are numerous studies involving decellularized tissue ECM, only a small portion of these demonstrated the effect of decellularization on the biophysical properties of hydrogels, such as mechanical stability and stiffness. It has been established in the literature that mechanical characteristics have an important impact on cell growth, motility, and tissue homeostasis . In Kingshott et al’s work, it was postulated that matrix stiffness has a direct effect on cell behavior as cells continuously remodel the matrix .…”

Assessing cell migration in hydrogels: An overview of relevant materials and methods

“…Natural tissue ECMs and most biological materials display complex mechanical properties, exhibiting time-dependent properties including viscoelasticity, viscoplasticity, non-linear elasticity and heterogenous behaviour depending on their location within the body [ 58 , 59 ]. The ECM can affect cell migration both regarding time and force scales of cell-ECM interactions where cells perceive the environment through their membrane and respond by reorganizing cytoskeletal elements.…”

Hydrogels to Recapture Extracellular Matrix Cues That Regulate Vascularization

“…47 Unlike elastic hydrogel substrates, viscoelastic hydrogels, based on reversible ionic or dynamic covalent bonds, result in stress relaxation and energy dissipation, leading to time-dependent cytoskeletal rearrangement and cell traction forces. 48,49 For instance, relaxed stress in 3D dynamic hydrogel networks facilitated integrin clustering and focal adhesion complex formation, followed by transferring mechanical signals to the actin component of the cytoskeleton. 50 This, in turn, enhanced cell contractility and hydrogel network deformations, as evidenced by the increased expression of phosphorylated myosin light chain and strong traction force as compared to those in nondynamic hydrogels.…”