Protein-like molecules called “polypeptoids” (or “peptoids,” for short) have great promise as precision building blocks for creating a variety of designer nanomaterials, like flexible nanosheets – ultrathin, atomic-scale 2D materials. They could advance a number of applications – such as synthetic, disease-specific antibodies and self-repairing membranes or tissue – at a low cost.
To understand how to make these applications a reality, however, scientists need a way to zoom in on a peptoid’s atomic structure. In the field of materials science, researchers typically use electron microscopes to reach atomic resolution, but soft materials like peptoids would disintegrate under the harsh glare of an electron beam.
Now, a team of Foundry users, working with staff, have adapted a technique that enlists the power of electrons to visualize a soft material’s atomic structure while keeping it intact.
Their study, published in the journal Proceedings of the National Academy of Sciences, demonstrates for the first time how cryo-EM (cryogenic electron microscopy), a Nobel Prize-winning technique originally designed to image proteins in solution, can be used to image atomic changes in a synthetic soft material. Their findings have implications for the synthesis of 2D materials for a wide variety of applications.
Unlike most synthetic polymers, peptoids can be made to have a precise sequence of monomer units, a common trait in biological polymers, such as proteins and DNA.
And like natural proteins, peptoids can grow or self-assemble into distinct shapes for specific functions – such as helices, fibers, nanotubes, or thin and flat nanosheets.
But unlike proteins, the molecular structure of peptoids is typically amorphous and unpredictable – like a pile of wet noodles. And untangling such an unpredictable structure has long been an obstacle for materials scientists.
So the researchers turned to cryo-EM, which flash-freezes the peptoids at a temperature of around 80 kelvins (or minus 316 degrees Fahrenheit) in microseconds. The ultracold temperature of cryo-EM locks in the structure of the sheet and also prevents the electrons from destroying the sample.
To protect soft materials, cryo-EM uses fewer electrons than conventional electron microscopy, resulting in ghostly black-and-white images. To better document what’s going on at the atomic level, hundreds of these images are taken. Sophisticated mathematical tools combine these images to make more detailed atomic-scale pictures.
For the study, the researchers fabricated nanosheets in solution from short peptoid polymers made of a chain of six hydrophobic monomers known as “aromatics,” connected to four hydrophilic polyether monomers. The hydrophilic or “water-loving” monomers are attracted to the water in the solution, while the hydrophobic or “water-hating” monomers avoid the water, orienting the molecules to form crystalline nanosheets that are only one-molecule thick (around 3 nanometers, or 3 billionths of a meter).
At the heart of the team’s discovery was their ability to rapidly iterate between materials synthesis and atomic imaging. The precision of peptoid synthesis, coupled with the researchers’ ability to directly image the placement of atoms using cryo-EM, allowed them to engineer the peptoid at the atomic level. To their surprise, when they created several new variations of the peptoid monomer sequence, the atomic structure of the nanosheet changed in a very orderly way.
Furthermore, when four additional variants of the peptoid nanosheet structure were imaged, the researchers noticed a remarkable uniformity across their atomic structure, and that the nanosheets shared the same shape of peptoid molecules.
Read the full press release.