Compressive forces driven by lateral actin fibers are a key to the nuclear deformation under uniaxial cell-substrate stretching

Cells sense the direction of mechanical stimuli including substrate stretching and show morphological and functional responses. The nuclear deformation with respect to the direction of mechanical stimuli is thought of as a vital factor in mechanosensitive intracellular signaling and gene transcription, but the detailed relationship between the direction of stimuli and nuclear deformation behavior is not fully solved yet. Here, we assessed the role of actin cytoskeletons in nuclear deformation caused by cell substrate stretching with different directions. Cells on a PDMS stretching chamber were subjected to a step-strain and changes of long- and short-axes of nucleus before and after stretching were evaluated in terms of nuclear orientation against the direction of stretching. Nuclei oriented parallel to the stretching direction showed elongation and shrinkage in the long and short axes, respectively, and vice versa. However, calculation of the aspect ratio (ratio of long- and short-axes) changes revealed orientation-depend nuclear deformation: The nucleus oriented parallel to the stretching direction showed a greater aspect ratio change than it aligned in the perpendicular direction of the stretching. A decrease in actin cytoskeletal tension significantly changed the nuclear deformation only in the short axis direction, thereby abolishing the orientation-depend deformation of the nucleus. These results suggest that lateral compressive forces exerted by the actin cytoskeleton is a key factor of orientation-depend deformation in short axis of the nucleus under the cell-substrate stretching condition, and may be crucial for mechano-sensing and responses to the cell-substrate stretching direction. •Effects of substrate-stretching directions on nuclear deformation were evaluated.•Nuclei oriented to the direction of cell substrate-stretching were highly deformed.•Lateral actin filament tension is a key of orientation-depend nuclear deformation.