For example, there is an optimal stress relaxation time intrinsic to the soft substrate to maximize cell spreading, whereas stress relaxation time does not affect cell spreading on stiff substrates. The viscous element of the tissue also can also contribute to cell behaviors. Recent evidences showed that viscous dissipation, or known as stress relaxation in the tissues may be involved in modulating proliferation, differentiation, and gene expression. But the measurement approaches described above can be used to extract stiffness value in different models wherever an elastic element is included. The viscoelastic model examines the time-dependent response of the biomaterials. Both viscoelastic and poroelastic models adopt dual characteristics of solids and fluids. Based on experimental observations, theoretical models depicting elastic, hyperelastic, viscoelastic, and poroelastic behaviors have been established. However, there are a handful of examples where elastic behaviors are dominant. As a result, cells and tissues usually exhibit dual characteristics belonging to both solids and liquids, and cannot be considered purely elastic or purely viscous most of the time. It should be noted that cells and tissues are a mixture of solid substances, consisting of insoluble biomolecules, and liquid, consisting of water and soluble biomolecules. The advances in these techniques have allowed dynamic measurement with high spatial resolution in vitro and in vivo. For local curvature measurement, image modalities such as computational tomography and optical microscopy have been used to acquire images of a region of interests, followed by the image analysis to determine the local curvature value at the desirable length scale. ECM architecture can be surveyed using several imaging modalities, including histological visualization, internal reflectance microscopy, and second harmonic generation. For viscosity measurement, rheometers/viscometers, optical traps and magnetic tweezers are commonly used. For stiffness measurement, methods implementing atomic force microscopy, magnetic tweezers, microfluidics, indentation, and magnetic resonance electrography, are commonly used depending on the length scale of the measurement. ![]() ![]() To study the relation between alterations in stiffness, viscosity, ECM architecture, and curvature, many techniques have been developed to measure those physical parameters of the micro-environment. Fibrosis results in elevated stiffness and altered ECM architecture. For example, during cancer development, increased stiffness, elevated extracellular fluid (ECF) viscosity, altered architecture of fibrillar ECM proteins in stroma and changed curvature are often observed in the micro-environment of solid tumors. During progression of many diseases, micro-environment of affected tissues is altered biochemically and biophysically, leading to changes of values in stiffness, viscosity, curvature, and ECM architecture. The ECM architecture can be characterized by parameters including density, pore size, and orientation of the ECM proteins. ![]() The most biologically relevant parameters of geometry at the molecular, cellular, and tissue scales are curvature and organization of constituent extracellular matrix (ECM) proteins. Viscosity defines the resistance experienced by an object when moving in an aqueous environment. Stiffness determines how deformable the substrate is where cells reside. The cues include, but not limited to, stiffness, viscosity, and geometry. In other words, mechanosignaling is an integral part of homeostasis, to maintain normal function of cells, and to govern cell fate.Ĭells sense mechanical cues and stimuli from their surrounding micro-environment. However, a vast body of studies in the past two decades laid the foundation of modern mechanobiology, the essence of which is the notion that not restricted to the aforementioned specialized cells, every cell type is equipped with the capacity to sense the mechanical cues and/or stimuli, and to interact with the micro-environment by generating mechanical forces. ![]() It had been widely known for a long time that specialized cells, such as sensory neurons of touch and hair cells in the ear can sense and respond to mechanical inputs from the environment and that another set of specialized cells, such as skeletal muscle cells, cardiomyocytes, and smooth muscle cells, are capable of generating mechanical forces.
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