Primary human MSCs treated with two different RNAi against SUN2

Cells resident in tissues must be resilient to the physical demands of their surroundings. Our current understanding of cellular mechano-signalling is largely based on static systems, but these models do not reproduce the dynamic nature of living tissue. Here, we examined the time-resolved response of primary human mesenchymal stem cells (hMSCs) to periods of cyclic tensile strain (CTS). We observed parallels between morphological changes following low-intensity strain (1 hour, 4% CTS at 1 Hz) and responses to increased substrate stiffness. However, as the strain regime was intensified (CTS at ≥ 2 Hz), we characterised a broad, structured and reversible protein-level response, even as transcription was apparently shut down. Regulation of the linker of nucleo- and cytoskeleton (LINC) complex proteins, and specifically of SUN domain-containing protein 2 (SUN2), was found to decouple mechano-transmission within the cell and hence isolate the nucleus from cellular deformation.