ReviewRole of nuclear mechanosensitivity in determining cellular responses to forces and biomaterials
Section snippets
Forces and biomaterial-generated physical cues perceived by cells
Cells in our body are always under force while the mode and degree are different with time and position. Endothelial cells in blood vessels experience constantly the pulsatile shear force of blood fluid [1]. Chondrocytes in cartilage are under dynamic compression loads whereas tendon and ligament cells experience primarily tensile forces to properly function [2]. Therefore, cells in our body (i.e. fibroblasts, adipocytes, neurons, myoblasts, chondrocytes, and osteoblasts) are keen to adopt the
Mechanosensitive machineries toward nucleus and their implications in cell fate change
The physiological forces perceived by cells are known to be in a wide range depending on the environments. For example, approximately 0.1–100 Pa (10–10000 nN/mm2) exerts on endothelial or blood cells [18] whereas a few hundreds of MPa (N/mm2) is reported for muscle, cartilage and bone [[19], [20], [21], [22]]. The external physical forces transmit through diverse sets of mechanosensitive cellular components that are physically connected, which includes integrin sets, adhesion complex,
Mechanosensitive ion channels
Apart from the integrin receptors, the mechanosensitive ion channels have long been implicated to take essential part in cellular mechanoreception of external cues (Fig. 2h). Ion channels allow the passage of ions across the cell membrane in response to a mechanical stimulus [98]. Among them, Piezo1 and Piezo2 are well-known mechanically activated cation channels that mediate cellular perception, proprioception, development and cell differentiation [99]. Mechanical stretch of cells activates
Concluding remarks
A wealth of studies has demonstrated the importance of biophysical signals of biomaterials and applied forces in cellular fate change. Mechanosensitive machineries of not only the cell surface receptors, the associated focal adhesion complex, and the actomyosin contractile machinery, but also of the LINC complex and the subnuclear mechanotransductory molecules recently discovered highlight the physical transmission of external signals toward nucleus. The translocation of transcription factors
Acknowledgments
This research was supported by the National Research Foundation of Korea (NRF) from Republic of Korea (Global Research Lab (GRL) Program 2015–0093829, NRF-2018R1A2B3003446, and Global Research Development Center (GRDC) Program NRF-2018K1A4A3A01064257).
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Nuclear transport of STAT6 determines the matrix rigidity dependent M2 activation of macrophages
2022, BiomaterialsCitation Excerpt :Moreover, we noted the enhanced expression of nuclear lamin A/C by increasing the substrate stiffness (Supplementary Fig. 5), which was consistent with the highly mechanosensitive adhesion-dependent non-immunogenic cells [63]. Because lamin A/C-mediated tight coupling between the nucleus and actin cytoskeletons regulates the substrate stiffness-dependent nuclear deformation [41,64], these results indicates that BMDMs also mechano-sense the substrate rigidity through the nuclear deformation and lamin A/C remodeling, which further implies that the nuclear shape of BMDMs could represent a level of intracellular mechanical stress induced by F-actin-mediated mechanosensation. To systematically assess the relationship between nuclear morphological changes and M2 activation, we introduced the nuclear flattening index (NFI), a three-dimensional shape factor that represents the nuclear deformation, indicating NFI >1 for the oblate nuclei and NFI <1 for the prolate nuclei (Fig. 3d).
Therapeutic tissue regenerative nanohybrids self-assembled from bioactive inorganic core / chitosan shell nanounits
2021, BiomaterialsCitation Excerpt :Nanohybrid sample significantly enhanced the gene expression of integrin sets (integrin α2, α3, and β1) as well as adaptor proteins (talin and focal adhesion kinase) that link the integrins to actin filaments, when compared to Chit, demonstrating the altered initial adhesion events of MSCs on the nanohybrid were largely mediated through the integrin (specifically, α2β1-and α3β1)-dependent focal adhesions [37]. On the other hand, the LINC complex (Sun1, Nesprin1, and Nesprin2) and nucleus lamin A/C, which directly transmit intracellular mechanical signals to a nucleus, were maintained at the same mRNA levels regardless of the substrate, implying these mechanotrasduction machineries might not be strongly involved in the events or the possibility of stimulation at protein (not gene) levels, which yet warrants further studies [38,39]. Albeit such a limitation in analysis tools, the qPCR array result suggests the nanohybrid should affect the initial cell adhesion number and spreading of MSCs through α2β1-and α3β1-mediated focal adhesions, messaging the possibility of accelerating further osteogenic cascades [40].
The cell as matter: Connecting molecular biology to cellular functions
2021, MatterCitation Excerpt :However, how physical/mechanical signals transduce from the extracellular microenvironment over a long distance to the nucleus is far from clear.72 Recently, the emerging concept of nuclear physical properties as a mechanoregulator of gene expression brings new insight into understanding how mechanical cues are transduced to the nucleus and how they influence nuclear mechanics, genome organization, and transcription (Figures 4A and 4C).73–80,81,82 More specifically, the nucleus can either serve as a downstream regulator of cytoplasmic signals or act as a direct effector independent of the cytoplasm (Figures 4B and 4C).