Year-end Sale % OFF 
Abstract
Studies of cellular mechano-signaling have often utilized static models that do not fully replicate the dynamics of living tissues. Here, we examine the time-dependent response of primary human mesenchymal stem cells (hMSCs) to cyclic tensile strain (CTS). At low-intensity strain (1 h, 4% CTS at 1 Hz), cell characteristics mimic responses to increased substrate stiffness. As the strain regime is intensified (frequency increased to 5 Hz), we characterize rapid establishment of a broad, structured and reversible protein-level response, even as transcription is apparently downregulated. Protein abundance is quantified coincident with changes to protein conformation and post-translational modification (PTM). Furthermore, we characterize changes to the linker of nucleoskeleton and cytoskeleton (LINC) complex that bridges the nuclear envelope, and specifically to levels and PTMs of Sad1/UNC-84 (SUN) domain-containing protein 2 (SUN2). The result of this regulation is to decouple mechano-transmission between the cytoskeleton and the nucleus, thus conferring protection to chromatin.
Highlights
Studies of cellular mechano-signaling have often utilized static models that do not fully replicate the dynamics of living tissues
We identify the Sad1/UNC-84 (SUN) domain-containing protein 2 (SUN2) as a strain-induced breakpoint in the linker of nucleoskeleton and cytoskeleton (LINC) complex of proteins that acts as a key mediator of intracellular mechano-transmission[13,19], enabling the nucleus to decouple from the cytoskeleton in response to intense strain
Primary human mesenchymal stem cells (hMSCs) were cultured on stiffness-controlled polyacrylamide hydrogels or silicone elastomer sheets that could be subjected to cyclic tensile strain (CTS); both substrates were collagen-I coated. hMSCs cultured for 3 days were found to spread increasingly on stiffer substrates over a physiological range (2–50 kPa; Fig. 1a, Supplementary Fig. 1a), as has been reported previously[1,20]
Summary
Studies of cellular mechano-signaling have often utilized static models that do not fully replicate the dynamics of living tissues. We characterize changes to the linker of nucleoskeleton and cytoskeleton (LINC) complex that bridges the nuclear envelope, and to levels and PTMs of Sad1/UNC84 (SUN) domain-containing protein 2 (SUN2). The result of this regulation is to decouple mechano-transmission between the cytoskeleton and the nucleus, conferring protection to chromatin. We identify the Sad1/UNC-84 (SUN) domain-containing protein 2 (SUN2) as a strain-induced breakpoint in the linker of nucleoskeleton and cytoskeleton (LINC) complex of proteins that acts as a key mediator of intracellular mechano-transmission[13,19], enabling the nucleus to decouple from the cytoskeleton in response to intense strain
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
