live nanoscale biology

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A new microscope developed in the Netherlands shows live real time nanoscale biological processes for the first time.

This means moving, working proteins in action.


It is a version of liquid phase electron microscopy. Technically it is "correlative cryo-liquid phase light/electron microscopy".


It has been used to view the complexation (self-assembly) of calcium phosphate with the protein fetuin-A. (See Figure 4 in the link above).
 
A new microscope developed in the Netherlands shows live real time nanoscale biological processes for the first time.

This means moving, working proteins in action.


It is a version of liquid phase electron microscopy. Technically it is "correlative cryo-liquid phase light/electron microscopy".


It has been used to view the complexation (self-assembly) of calcium phosphate with the protein fetuin-A. (See Figure 4 in the link above).
What are the useful possibilities of this?
 
What are the useful possibilities of this?
One very promising application is a better understanding of proteins built from subunits. These are typically trimers or tetramers consisting of 3 or 4 "almost identical" subunits, which previously required x-ray crystallography or other complex and time consuming methods to decipher. Many membrane bound proteins are assembled from subunits, for example neurotransmitter receptors and ion channels.

There are bigger structures assembled from even more subunits, for example microtubules which self-assembly from 9 or 13 nearly identical sub-proteins. Other examples might include the actin and myosin in muscles.

Another promising application is understanding why some otherwise unrelated proteins clump together under certain conditions. For example this happens in Alzheimers. And also, why certain proteins misfold when they touch other proteins, which happens with prions.
 
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This kind of thing is pretty common by now.

1733459863936.webp


In this pic a computer is used to identify type and orientation of cell surface proteins. This type of technology is already in widespread commercial use.

But you can plainly see, that there are plenty of proteins it doesn't identify (which are the unmarked green dots).

This new microscopy lets us zoom in on those unmarked proteins by a factor of 50. It makes their shapes and orientations perfectly clear.

Furthermore, purifying any such protein on a molecular grid (which means anything from sucrose to graphene) lets us take pictures of the molecule from many angles simultaneously - so all its twists and turns become visible.

Purifying embedded proteins is not necessarily easy, but they can sometimes be extracted from the membrane with "light tweezers", and there is a new two-molecule calcium ejection procedure that can dissolve the immediately adjoining membrane, freeing the protein.

These techniques are very promising, they're not yet commercially feasible but they will be soon.
 
This kind of thing is pretty common by now.

View attachment 1050661

In this pic a computer is used to identify type and orientation of cell surface proteins. This type of technology is already in widespread commercial use.

But you can plainly see, that there are plenty of proteins it doesn't identify (which are the unmarked green dots).

This new microscopy lets us zoom in on those unmarked proteins by a factor of 50. It makes their shapes and orientations perfectly clear.

Furthermore, purifying any such protein on a molecular grid (which means anything from sucrose to graphene) lets us take pictures of the molecule from many angles simultaneously - so all its twists and turns become visible.

Purifying embedded proteins is not necessarily easy, but they can sometimes be extracted from the membrane with "light tweezers", and there is a new two-molecule calcium ejection procedure that can dissolve the immediately adjoining membrane, freeing the protein.

These techniques are very promising, they're not yet commercially feasible but they will be soon.

 

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