Phenotypic plasticity, or adaptability, of a cell determines its ability to survive and function within changing cellular environments. Changes in the mechanical environment, ranging from stiffness of the extracellular matrix (ECM) to physical stress such as tension, compression, and shear, are critical environmental cues that influence phenotypic plasticity and stability. Furthermore, an exposure to a prior mechanical signal has been demonstrated to play a fundamental role in modulating phenotypic changes that persist even after the mechanical stimulus is removed, creating stable mechanical memories. In this mini review, our objective is to highlight how the mechanical environment alters both phenotypic plasticity and stable memories through changes in chromatin architecture, mainly focusing on examples in cardiac tissue. We first explore how cell phenotypic plasticity is modulated in response to changes in the mechanical environment, and then connect the changes in phenotypic plasticity to changes in chromatin architecture that reflect short-term and long-term memories. Finally, we discuss how elucidating the mechanisms behind mechanically induced chromatin architecture that lead to cell adaptations and retention of stable mechanical memories could uncover treatment methods to prevent mal-adaptive permanent disease states.

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Mechanically induced alterations in chromatin architecture guide the balance between cell plasticity and mechanical memory

Chromatin modifications influence all the nuclear functions that are templated by the DNA, and regulate when and how the genome should be expressed and copied As chromatin states are reversible in nature, elaborate mechanisms have evolved to ensure the stable inheritance and maintenance of chromatin states that define differentiation stage- and cell type–specific gene expression patterns Importantly, these heritable marks, termed epigenetic modifications, can also be reprogrammed by environmental signals The heritability and reversibility of chromatin modifications thus regulate developmental processes in multicellular organisms by balancing between the robust maintenance of the phenotype against environmental perturbations and phenptypic plasticity during adaptive responses In this process chromatin has been envisaged to function as a platform for both buffering against and integrating environmental cues, enabling the propagation of transient signals over time In this chapter we will discuss the brief history and recent advances of chromatin-based processes to provide an overview about the role of chromatin in development and the deregulation of these processes in diseases

A Brief Introduction to Chromatin Regulation and Dynamics

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A Brief Introduction to Chromatin Regulation and Dynamics