EV(Extracellular Vescicle)가 matrix를 거쳐갈 수 있는 mechanism

https://phys.org/news/2020-06-unveils-mechanism-long-distance-cell.html

 

An extracellular vesicle—a nanoparticle released by cells—can use jerky movements similar to a car weaving in and out of traffic to navigate the obstacle-filled environment outside of cells

"Although EVs were discovered over 30 years ago, many believed that EVs were cellular junk that was trapped in the extracellular matrix," said senior author Jae-Won Shin, UIC assistant professor of pharmacology and bioengineering at the College of Medicine. "Within the last 10 years, the field has learned that EVs aren't junk. They play a critical role in sending signals for long-distance communication between cells."

To understand how billions of EVs navigate through the matrix, Shin's lab used improved imaging, vesicle labeling and motion capturing technologies that weren't available decades ago.

"We saw that the gaps in the matrix were smaller than the size of EVs and thought travel would be difficult," Shin said. "It was a surprise when we observed that the EVs traveled much more readily than we thought in certain conditions."

The researchers utilized an artificial matrix, called a hydrogel, to study whether its structure played a role in EV navigation. They customize the hydrogel's stiffness and how well the hydrogel could relax after being stressed by an object in order to make the hydrogel more or less like the matrix in the body.

"The hydrogel needed to have a stiff backbone to provide some sort of structure, but after a stress it also had to relax enough to rearrange itself over time, which allowed the EVs to move around. The interesting finding was that this ability to move that occurred for EVs in some materials did not occur for synthetic particles of similar size."

When aquaporin-1—a membrane protein that allows water in and out of EVs—stopped functioning, the EVs became stuck. The permeation of water through aquaporin-1 in the membrane was essential for EVs to slip through the hydrogel gaps.

"There are a range of diseases that undergo substantial changes in their environment. In fibrosis and some cancers, the tissues and matrix become more rigid as time progresses. In some cancers, the distribution of EVs have led to disease spreading," he said. "So, understanding how EVs are dispersed is critical for developing these cell-free therapeutics and stopping disease progression."

 

 

membrane의 original state는 EV보다 작다. 그러나 artifiacial Cell matrix인 hydrogel이 물렁하여 충격을 줬을 때 deformation으로부터 회복하는 시간이 길면, 그 사이에 EV가 지나갈 수 있게 된다. 거기다가 EV에 있는 AQP1이라는 water permeable membrane이 물을 내뱉음으로써 defomability가 증가한다. 

 

 

reference

Stephen Lenzini et al. Matrix mechanics and water permeation regulate extracellular vesicle transport, Nature Nanotechnology (2020). DOI: 10.1038/s41565-020-0636-2