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

Abstract

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.

Mechanical activation and expression of HSP27 in epithelial ovarian cancer

“…Mechanical memory works by altering the nuclear architecture of a cell, leading to epigenetic changes, and eventually changing the phenotype of the cells. These changes can be reversible or irreversible, depending on the type of mechanical cue and also the duration of the cue 53 , 54 Once SKOV-3 cells were placed in the 3D TME device, they demonstrated mechanical memory represented by increased HSP27 expression in the experimental groups of cells that had been strained for 24h or 72h (Fig. 4 D).…”

Vaccinia virus infection induces concurrent alterations in host chromatin architecture, accessibility, and gene expression

“…The architecture of the genome, including its compartmentalization, chromatin contacts, conformation, and accessibility, is as fundamental to understanding the function of a particular genomic loci as its sequence. Indeed, investigation of 3D chromatin structure may be paramount to deciphering disease-states, aberrant cellular behavior, and the impact of environmental perturbations, including pathogen exposures, all of which have functional implications, including dysregulation of gene expression 13,[47][48][49][50] . Further, pathogen-induced changes in host chromatin features may have far-reaching implications for development of appropriate and efficacious countermeasures including vaccine development.…”

To be or not to be - Decoding the Trabecular Meshwork Cell Identity

“…Thus it is feasible to infer that while mechanical cues may drive hTM cell function as a function of substrate properties, the initial culture conditions in which these cells were first isolated and expanded 3/13 may have also profound impact on selection of cells for propagation, proliferation, and (de-)differentiation. That mechanical memory and plasticity exists in maintaining cell identity through epigenetic regulation has been previously postulated [56][57][58][59][60][61][62] .…”

“…However, whether such a phenomenon exists in primary hTM cells remains to be further determined. Further, emerging evidence suggests chromatin remodeling implicating significant changes to cellular and epigenetic plasticity may significantly alter cell fate with prolonged exposure to rigid culture environments such as tissue culture plastic [61][62][63][64] . Since all primary hTM cells are primarily cultured and expanded on rigid plastic substrates, it is only natural to infer that the process of divergence in cell identity as observed in this study likely starts immediately after initial isolation.…”