Fig. 8.

Schematic of the hypothesised mechanism.

Cellular sensing of stiff substrates may alter nuclear shape (blue) by increasing tension through the nucleus-cytoskeleton link (magenta) further promoting morphological and phenotypical cell deregulations. Uncoupling the nucleus from the cytoskeleton either by nesprin disconnection (DN-KASH) or pharmacological disruption of the cytoskeleton (Cd) alleviates nuclear tension and recovers healthy cell morphology and phenotype. Cd, cytoskeletal disruptor; ECM, extracellular matrix; DN-KASH, negative dominant nesprin peptide containing a Klarsicht/abnormal nuclear anchorage-1/Syne homology domain.