(19g) Invited: Nuclear Mechanics in Cell Migration and Tissue Development

The shape of the nucleus is characteristic of cell type, and becomes abnormal in a number of human pathologies. Shaping the nucleus represents a particular challenge for the cell as it migrates through tight spaces in tissue, because of its large size and resistance to deformation. We designed experiments in which cells migrate from 1-D fibronectin lines to 2-D fibronectin patterns to examine how nuclear shape evolves with changes in cell morphology during cell migration. We observed that nuclear shape only changes when there are dynamic changes in cell shape. Coupled with the observation that nuclei retain shape upon removal of the surrounding cell, and that nuclear flattening correlates with cell spreading without requiring actomyosin activity, we propose the concept that the nucleus is shaped by dynamic stresses transmitted from the moving cell boundary to the nucleus through friction in the intervening F-actin network. This model for nuclear shaping explains the observed relationship between the shape of the cell and the shape of the nucleus. I will conclude with results from some of our recent efforts on understanding the role of the nucleus in epithelial tissue development and mechanics.