Science Cover: Amazing!

First come to a moving picture to feast your eyes~

What is this, this is the first-hand on-the-spot information sent by the T-cell anti-cancer front line~ A T-cell blast is close to the body, and the cancer cells die instantly~ The death sticker is true

T cells kill cancer cells by "close-up poisoning"

Of course, cancer cells are not passively waiting to die.

How do cancer cells fight back? Using the idea of ​​​​filling what is missing, T cells have opened holes in the cell membrane.

Not to mention, this trick is really basic

There is a protein called the endosome sorting complex required for transport (ESCRT) , which is involved in the remodeling and damage repair of cell membranes.

Well, I think everyone should realize that this study is to verify that ESCRT is also involved in cancer cells repairing membrane damage caused by T-cell perforin, and the verification should be successful.

So without further ado, let me explain this fun mechanism directly to you

Look at the picture first

Under the action of ESCRT, the damaged and perforated cell membrane forms buds, and then "booms" off (this step is doubtful)! This is the broken membrane, and we are a good cell again

However, this study only observed some phenomena, and it cannot be said that the whole process is done

Cancer cells are more sensitive to perforin/granzyme killing after ESCRT knockout

In addition, ESCRT will not be the only means of resistance for cancer cells.

It's all about watching movies~

T cells are shown in magenta in the image below, cancer cells are shown in grey/green, and the bright orange-red is a high-concentration dye propidium iodide (PI) that diffuses rapidly through membrane perforations and binds to the cytoplasm and nucleus.

So where is ESCRT?

Look here~ Do you see a little bright green between the T cells and the cancer cells? That is ESCRT labeled with fluorescent protein

There is also an exploded view here

The researchers also recorded footage of ESCRT sticking to T cells

The researchers speculate that this should be the shedding membrane fragments containing ESCRT, because it contains T cell receptor ligands, so it sticks to T cells
.

Most importantly, in order to understand what happened between T cells and cancer cells, the researchers also used cryogenic fluorescence imaging to fix the moment when the two sides fought, and used electron microscopy to reconstruct 3D models
.

Come see this beautiful detail
.

 

Even cell substructures can be restored one by one
.

References:

[1] https://

[2] AJ Jimenez, P.
Maiuri, J.
Lafaurie-Janvore, S.
Divoux, M.
Piel, F.
Perez, ESCRT machinery is required for plasma membrane repair.
Science343, 1247136 (2014).

[3]LL Scheffer, SC Sreetama, N.
Sharma, S.
Medikayala, KJ Brown, A.
Defour, JK Jaiswal, Mechanism of Ca2+-triggered ESCRT assembly and regulation of cell membrane repair.
Nat.
Commun.
5, 5646 (2014 ).

First come to a moving picture to feast your eyes~

First come to a moving picture to feast your eyes~

What is this, this is the first-hand on-the-spot information sent by the T-cell anti-cancer front line~ A T-cell blast is close to the body, and the cancer cells die instantly~ The death sticker is true
.

What is this, this is the first-hand on-the-spot information sent by the T-cell anti-cancer front line~ A T-cell blast is close to the body, and the cancer cells die instantly~ The death sticker is true
.

T cells kill cancer cells by "close-up poisoning"
.
T cells will stick to cancer cells, release perforin, "open holes" in the cell membrane of cancer cells, and then send granzymes into the cancer cells to achieve instant explosion
.

T cells kill cancer cells by "close-up poisoning"
.
T cells will stick to cancer cells, release perforin, "open holes" in the cell membrane of cancer cells, and then send granzymes into the cancer cells to achieve instant explosion
.
T cells will stick to cancer cells, release perforin, "open holes" in the cell membrane of cancer cells, and then send granzyme into the cancer cells to achieve instant explosion

Of course, cancer cells are not passively waiting to die.
A new study, published this week in the journal Science, used advanced cryogenic imaging techniques and focused ion beam scanning electron microscopy (FIB-SEM) at 8nm resolution.
It reproduces the most subtle battlefield details of this anti-cancer war, as well as the weak resistance of cancer cells [1]
.
The paper is also the cover of this week's Science, with corresponding authors Ira Mellman and Alex T.
Ritter from Genentech
.

Of course, cancer cells are not passively waiting to die.
A new study, published this week in the journal Science, used advanced cryogenic imaging techniques and focused ion beam scanning electron microscopy (FIB-SEM) at 8nm resolution.
It reproduces the most subtle battlefield details of this anti-cancer war, as well as the weak resistance of cancer cells [1]
.
The paper is also the cover of this week's Science, with corresponding authors Ira Mellman and Alex T.
Ritter from Genentech
.
A new study, published this week in the journal Science, uses advanced cryogenic imaging techniques and focused ion beam scanning electron microscopy (FIB-SEM) to recreate the tiniest details of the battle against cancer at 8nm resolution.
details of the battlefield, and the weak resistance of cancer cells

How do cancer cells fight back? Using the idea of ​​​​filling what is missing, T cells have opened holes in the cell membrane.
Can we fill the holes before they are killed by granzymes?

How do cancer cells fight back? Using the idea of ​​​​filling what is missing, T cells have opened holes in the cell membrane.
Can we fill the holes before they are killed by granzymes?

Not to mention, this trick is really basic
.

Not to mention, this trick is really basic
.

There is a protein called the endosome sorting complex required for transport (ESCRT) , which is involved in the remodeling and damage repair of cell membranes.
Previous studies have found that ESCRT can repair bacteria caused by pore-forming toxins, mechanical damage and lasers.
pores in the plasma membrane [2,3]
.

There is a protein called the endosome sorting complex required for transport (ESCRT) , which is involved in the remodeling and damage repair of cell membranes.
Previous studies have found that ESCRT can repair bacteria caused by pore-forming toxins, mechanical damage and lasers.
pores in the plasma membrane [2,3]
.
Endosomal sorting complex required for transport (ESCRT) Previous studies have found that ESCRT can repair small pores in the plasma membrane caused by bacterial porogens, mechanical damage, and laser light

Well, I think everyone should realize that this study is to verify that ESCRT is also involved in cancer cells repairing membrane damage caused by T-cell perforin, and the verification should be successful.
.
.

Well, I think everyone should realize that this study is to verify that ESCRT is also involved in cancer cells repairing membrane damage caused by T-cell perforin, and the verification should be successful.
.
.

So without further ado, let me explain this fun mechanism directly to you
.

So without further ado, let me explain this fun mechanism directly to you
.

Look at the picture first
.
When perforin creates perforin pores on the surface of cancer cells, ESCRT accumulates at the site of the pores
.

Look at the picture first
.
When perforin creates perforin pores on the surface of cancer cells, ESCRT accumulates at the site of the pores
.
When perforin creates perforin pores on the surface of cancer cells, ESCRT accumulates at the site of the pores
.

Under the action of ESCRT, the damaged and perforated cell membrane forms buds, and then "booms" off (this step is doubtful)! This is the broken membrane, and we are a good cell again
.

Under the action of ESCRT, the damaged and perforated cell membrane forms buds, and then "booms" off (this step is doubtful)! This is the broken membrane, and we are a good cell again
.
Under the action of ESCRT, the damaged and perforated cell membrane forms buds, and then "booms" off.

However, this study only observed some phenomena, and it cannot be said that the whole process is done
.
Combined with the results of past studies, this is basically the case.
In the study, it was also observed that cancer cells were more sensitive to perforin and granzyme after knocking out ESCRT
.

However, this study only observed some phenomena, and it cannot be said that the whole process is done
.
Combined with the results of past studies, this is basically the case.
In the study, it was also observed that cancer cells were more sensitive to perforin and granzyme after knocking out ESCRT
.

Cancer cells are more sensitive to perforin/granzyme killing after ESCRT knockout

Cancer cells are more sensitive to perforin/granzyme killing after ESCRT knockout

In addition, ESCRT will not be the only means of resistance for cancer cells.
Researchers believe that cancer cells may also engage in repair engineering by endocytosing part of the perforated membrane and secreting lysosomes
.
These require further research
.

In addition, ESCRT will not be the only means of resistance for cancer cells.
Researchers believe that cancer cells may also engage in repair engineering by endocytosing part of the perforated membrane and secreting lysosomes
.
These require further research
.
The researchers believe that cancer cells may also engage in repair engineering by endocytosing perforated parts of the membrane and secreting lysosomes

It's all about watching movies~

It's all about watching movies~

T cells are shown in magenta in the image below, cancer cells are shown in grey/green, and the bright orange-red is a high-concentration dye propidium iodide (PI) that diffuses rapidly through membrane perforations and binds to the cytoplasm and nucleus.
nucleic acid within
.

T cells are shown in magenta in the image below, cancer cells are shown in grey/green, and the bright orange-red is a high-concentration dye propidium iodide (PI) that diffuses rapidly through membrane perforations and binds to the cytoplasm and nucleus.
nucleic acid within
.

So where is ESCRT?

So where is ESCRT?

Look here~ Do you see a little bright green between the T cells and the cancer cells? That is ESCRT labeled with fluorescent protein
.
The ESCRT reached the perforation site within 30 to 60 seconds after the influx of propidium iodide
.

Look here~ Do you see a little bright green between the T cells and the cancer cells? That is ESCRT labeled with fluorescent protein
.
The ESCRT reached the perforation site within 30 to 60 seconds after the influx of propidium iodide
.

There is also an exploded view here
.

There is also an exploded view here
.

The researchers also recorded footage of ESCRT sticking to T cells
.

The researchers also recorded footage of ESCRT sticking to T cells
.

The researchers speculate that this should be the shedding membrane fragments containing ESCRT, because it contains T cell receptor ligands, so it sticks to T cells
.

The researchers speculate that this should be the shedding membrane fragments containing ESCRT, because it contains T cell receptor ligands, so it sticks to T cells
.

Most importantly, in order to understand what happened between T cells and cancer cells, the researchers also used cryogenic fluorescence imaging to fix the moment when the two sides fought, and used electron microscopy to reconstruct 3D models
.

Most importantly, in order to understand what happened between T cells and cancer cells, the researchers also used cryogenic fluorescence imaging to fix the moment when the two sides fought, and used electron microscopy to reconstruct 3D models
.

Come see this beautiful detail
.

Come see this beautiful detail
.

 

Even cell substructures can be restored one by one
.

Even cell substructures can be restored one by one
.

References:

References:

[1] https:// https:// AJ Jimenez, P.
Maiuri, J.
Lafaurie-Janvore, S.
Divoux, M.
Piel, F.
Perez, ESCRT machinery is required for plasma membrane repair.
Science343, 1247136 (2014).

[2] AJ Jimenez, P.
Maiuri, J.
Lafaurie-Janvore, S.
Divoux, M.
Piel, F.
Perez, ESCRT machinery is required for plasma membrane repair.
Science343, 1247136 (2014).

[3]LL Scheffer, SC Sreetama, N.
Sharma, S.
Medikayala, KJ Brown, A.
Defour, JK Jaiswal, Mechanism of Ca2+-triggered ESCRT assembly and regulation of cell membrane repair.
Nat.
Commun.
5, 5646 (2014 ).

[3]LL Scheffer, SC Sreetama, N.
Sharma, S.
Medikayala, KJ Brown, A.
Defour, JK Jaiswal, Mechanism of Ca2+-triggered ESCRT assembly and regulation of cell membrane repair.
Nat.
Commun.
5, 5646 (2014 )

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