Abstract
Mesenchymal stem cells (MSCs) show tremendous promise as a cell source for tissue engineering and regenerative medicine, and are understood to be mechanosensitive to external mechanical environments. In recent years, increasing evidence points to nuclear envelope proteins as a key player in sensing and relaying mechanical signals in MSCs to modulate cellular form, function, and differentiation. Of particular interest is the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex that includes nesprin and SUN. In this review, the way in which cells can sense external mechanical environments through an intact nuclear envelope and LINC complex proteins will be briefly described. Then, we will highlight the current body of literature on the role of the LINC complex in regulating MSC function and fate decision, without and with external mechanical loading conditions. Our review and suggested future perspective may provide a new insight into the understanding of MSC mechanobiology and related functional tissue engineering applications.
Highlights
Cellular sensing and response to changes in extracellular environments, biochemical and mechanophysical, are critical for cell growth and function
Linker of Nucleoskeleton and Cytoskeleton (LINC) complex The nuclear membrane is composed of an inner nuclear membrane (INM) and an outer nuclear membrane (ONM), which are separated by a ~ 40 nm gap known as the perinuclear space (PNS) [5]
The lamina is composed of lamin A/C proteins that are mechanically connected to varying cytoskeletal proteins via the LINC complex (Fig. 1a) [6]
Summary
Cellular sensing and response to changes in extracellular environments, biochemical and mechanophysical, are critical for cell growth and function. The LINC complex and related nuclear envelope-actin linkage have a potential to affect the functions of centrosomes [17] and meiotic chromosomes [18] to regulate cell division and replication.
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