Figure 2. Potential mechanisms of nuclear mechanosensing.

Schematic illustration of how force-induced nuclear deformation could modulate expression of mechano-responsive genes. (A) This example shows a cell exposed to a uniaxial stretch, resulting in nuclear deformation by forces transmitted from focal adhesions through the (actin) cytoskeleton to the nucleus. (B) Potential molecular mechanisms for nuclear mechanosensing: (i) Opening of chromatin structures under force, enabling access of transcriptional regulators to the chromatin. (ii) Chromatin detachment from the lamina, freeing genes from the often transcriptionally repressive nuclear periphery. This process could also result in further changes in chromatin structure, promoting access to transcriptional regulators. (iii) Stretching the lamina could result in conformational changes or partial unfolding of lamins, altering their interaction with transcriptional regulators. Shown here is the release of transcription factors, which can then interact with their target genes. Phosphorylation and other post-translational modifications of nuclear envelope proteins could further contribute to nuclear mechanosensing.