Tailoring Cellular Function: The Contribution of the Nucleus in Mechanotransduction

Abstract

Cells sense a variety of different mechanochemical stimuli and promptly react to such signals by reshaping their morphology and adapting their structural organization and tensional state. Cell reactions to mechanical stimuli arising from the local microenvironment, mechanotransduction, play a crucial role in many cellular functions in both physiological and pathological conditions. To decipher this complex process, several studies have been undertaken to develop engineered materials and devices as tools to properly control cell mechanical state and evaluate cellular responses. Recent reports highlight how the nucleus serves as an important mechanosensor organelle and governs cell mechanoresponse. In this review, we will introduce the basic mechanisms linking cytoskeleton organization to the nucleus and how this reacts to mechanical properties of the cell microenvironment. We will also discuss how perturbations of nucleus–cytoskeleton connections, affecting mechanotransduction, influence health and disease. Moreover, we will present some of the main technological tools used to characterize and perturb the nuclear mechanical state.

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

“…217 The nuclear LINC complex is located below the nuclear envelope and contains lamin, nesprins, and Sad1 and UNC-84 (SUN) proteins. 218,219 Mechanical deformation of the nucleus induces changes in chromatin organization by a mechanism depending on intracellular calcium release and leading to softening of the nuclear envelope, which is crucial in preventing stretch-induced DNA damage. 220,221 There is also a linear scaling relation between collagen content in the ECM and lamin A contents in the nuclear envelope across different stages of fibrosis, indicating that ECM conditions reflect nuclear mechanics and signaling.…”

Cytoskeleton Response to Ionizing Radiation: A Brief Review on Adhesion and Migration Effects

“…However, it is important to consider that the augmentation of cytoskeletal stiffness could be not the direct consequence of the nuclear expansion, but the cause of this phenomenon. In fact, contractile actin structures, thanks to the LINC complex (Linker of Nucleoskeleton and CSK), can directly transmit mechanical forces to the nucleus and the genome at its interior, change its shape and regulate gene expression [ 75 ]. In particular, it has been demonstrated that a strict correlation exists between CSK organization, cell spreading and nuclear shape [ 76 ], indicating that the increased content of F-actin and the cell stiffening could be responsible for changes in nuclear shape.…”

Chronic lung diseases: entangled in extracellular matrix

“…Almost three decades ago, INGBER [73][74][75] coined the term "tensegrity" (tension integration) to describe the information-conducting mechanism through which deformation of cells causes disruption of the self-supporting cortical actin cytoskeleton that is relayed throughout the cell and contributes to mechanosignalling. The actin cytoskeleton also physically interacts with the nuclear lamina, and in this way directly changes the chromatin structure and thus gene expression [76,77]. The tensegrity of cyclically stretched substrates (lungs) has been mathematically modelled [78].…”