Nuclear mechanics during and after constricted migration

Cell migration through very narrow spaces in tissues has been seen in both physiological and pathological contexts. For example, immune cells squeeze through the vasculature and the extracellular matrix to reach wound or disease sites, and similarly, cancer cells crawl through interstices in tissues to invade tumor-free regions. The bulky and stiff nucleus of a cell is a barrier to such constricted migration—with smaller pores exponentially more difficult for passage. Cells must actively deform their nuclei to squeeze through constrictions, and this involves the stress-generating cytoskeleton. Here we review: (1) nuclear structures and morphological regulation, (2) proposed mechanisms that drive constricted migration, (3) short-term consequences such as nuclear envelope (NE) rupture and DNA damage during such process, (4) biophysical factors that facilitate NE rupture, and (5) long-term consequences such as genomic variation caused by repetitive NE rupture. Both experimental results and modeling are provided with the intention to better understand constricted migration.