Cell migration through narrow interstitial space in tissues is commonly seen in both physiological and pathological conditions. For example, immune cells have to squeeze through vasculature and extracellular matrix to...Cell migration through narrow interstitial space in tissues is commonly seen in both physiological and pathological conditions. For example, immune cells have to squeeze through vasculature and extracellular matrix to reach the wound or diseased sites, and similarly cancer cells need to crawl through porous space in tissues to invade surrounding tumor-free regions. Therefore, the bulky stiff nucleus in the cell becomes a barrier during constricted migration making such process pore-size dependent with smaller pores exponentially alleviate the passage capability. However, in some cases, cells can actively deform their nuclei to squeeze through constrictions although some price needs to be paid. In this review, we focus on:(1) nuclear structures and morphological regulations,(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 the constricted migration.展开更多
基金the National Institutes of Health National Cancer Institute under Physical Sciences Oncology Center Award U54 CA193417National Heart Lung and Blood Institute Award R21 HL128187the US-Israel Binational Science Foundation, and National Science Foundation grant agreement CMMI 15-48571.
文摘Cell migration through narrow interstitial space in tissues is commonly seen in both physiological and pathological conditions. For example, immune cells have to squeeze through vasculature and extracellular matrix to reach the wound or diseased sites, and similarly cancer cells need to crawl through porous space in tissues to invade surrounding tumor-free regions. Therefore, the bulky stiff nucleus in the cell becomes a barrier during constricted migration making such process pore-size dependent with smaller pores exponentially alleviate the passage capability. However, in some cases, cells can actively deform their nuclei to squeeze through constrictions although some price needs to be paid. In this review, we focus on:(1) nuclear structures and morphological regulations,(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 the constricted migration.
