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Living cells are out of equilibrium active materials. Cell-generated forces are transmitted across the cytoskeleton network and to the extracellular environment. These active force interactions shape cellular mechanical behavior, trigger mechano-sensing, regulate cell adaptation to the microenvironment and can affect disease outcomes. In recent years, the mechanobiology community has witnessed the emergence of many experimental and theoretical approaches to study cells as mechanically active materials. In this review, we highlight recent advancements in incorporating active characteristics of cellular behavior at different length scales into classic viscoelastic models by either adding an active tension-generating element or by adjusting the resting length of an elastic element in the model. Summarizing the two groups of approaches, we will review the formulation, and application of these models to understand cellular adaptation mechanisms in response to various types of mechanical stimuli, such as the effect of extracellular matrix properties and external loadings or deformations. 

Epithelial cells experience long lasting loads of different magnitudes and rates. How they adapt to these loads strongly impacts tissue health. Yet, much remains unknown about their stress evolution under sustained strain. Here, by subjecting cell pairs to sustained strain, we report a bimodal stress response, where in addition to the typically observed stress relaxation, a subset of cells exhibits a dynamic tensioning process with significant elevation in stress within 100s, resembling active pulling-back in muscle fibers. Strikingly, the fraction of cells exhibiting tensioning increases with increasing strain rate. The tensioning response is accompanied by actin remodeling, and perturbation to actin abrogates it, supporting cell contractility’s role in the response. Collectively, our data show that epithelial cells adjust their tensional states over short timescales in a strain-rate dependent manner to adapt to sustained strains, demonstrating that the active pulling-back behavior could be a common protective mechanism against environmental stress.