Extracellular Matrix Viscoelasticity: A Dynamic Regulator of Cellular Behavior

The extracellular matrix (ECM) is a three-dimensional network of polysaccharides and proteins that provides biochemical signals and structural rigidity to cells. In addition to structural support, the ECM provides dynamic mechanical properties such as viscoelasticity. Scientifically, viscoelasticity is the time-dependent response of materials under stress. Due to the viscoelastic behavior of the ECM, viscoelasticity plays a critical role in regulating and stimulating cellular behaviors such as adhesion, proliferation, differentiation, and migration, as well as tissue morphogenesis and remodeling. Scientific knowledge about viscoelasticity usually originates from materials science where physical parameters are well defined. Hence, understanding materials' physical/mechanical behaviors (especially biomaterials in biological contexts) and mathematical modeling related to viscoelasticity are important to achieve useful results. On the other hand, recent advances in the development of biophysical instruments for measuring viscoelasticity have revealed a strong link between material properties and physiological systems and have emerged as important diagnostic tools for investigating the viscoelastic behavior of cells and tissues. Therefore, this review, focusing on matrix viscoelasticity, explains the viscoelastic nature of cells/tissues, examines the impact of matrix viscoelasticity on cellular processes, reviews the role of engineered biomaterials in improving cellular behaviors, and finally discusses modern experimental techniques for measuring viscoelasticity at the cellular level.