Actin and microtubules play distinct roles in governing the anisotropic deformation of cell nuclei in response to substrate strain.

Physical forces arising in the cellular microenvironment have been hypothesized to play a major role in governing cell function. Moreover, it is thought that gene regulation may be sensitive to nuclear deformations taking place in response to extracellular forces over short and long timescales. Although nuclear responses to mechanical stimuli over long timescales are relatively well studied, the short-term responses are poorly understood. Therefore, to characterize the short-term instantaneous deformation of the nucleus in a mechanically dynamic environment, we exposed MDCK epithelial monolayers to varying mechanical strain fields. The results reveal that nuclei deform anisotropically in response to substrate strain, specifically, the minor nuclear axis is significantly more deformable than the major axis. We show that upon microtubule depolymerization, nuclear deformation anisotropy completely disappears. Moreover, the removal of actin causes a significant increase in nuclear deformation along the minor axis and a corresponding increase in mechanical anisotropy. The results demonstrate that the nucleus deforms in a manner that is very much dependent on the direction of strain and the characteristics of the strain field. Actin and microtubules also appear to play distinct roles in controlling the anisotropic deformation of the nucleus in response to mechanical forces that arise in the cellular microenvironment.