Many people are vaguely familiar with the basic concepts concerning DNA: it is the genetic material in every one of our cells that make us who we are. We inherit our DNA from our parents, who in turn inherited it from their parents, etc etc. Most people also understand the basic structure of DNA: it is a very LONG sequence of nucleotides, referred to as C, G, T, A. If we think of DNA as a necklace, and the C, G, T, and A as beads on this necklace, it is the specific sequence of these C’s, G’s, T’s, and A’s on this necklace that makes us all unique. This may be where many non-scientists’ understanding of DNA ends. DNA on its own doesn’t do that much – its when the sequence of a portion of the DNA is used in the transcription of RNA and thus translation to proteins that many aspects of life really begin. In short, the DNA code (specific sequences of C, G, T, and A) is used to make lots of different proteins. Proteins have many different and complex uses in our bodies, so I’m going to refer to the NIH definition, since I can’t do any better:
Proteins are large, complex molecules that play many critical roles in the body. They do most of the work in cells and are required for the structure, function, and regulation of the body’s tissues and organs.
Proteins are made up of hundreds or thousands of smaller units called amino acids, which are attached to one another in long chains. There are 20 different types of amino acids that can be combined to make a protein. The sequence of amino acids determines each protein’s unique 3-dimensional structure and its specific function.
Because proteins are so important in many aspects of life, many scientists work to better understand the structure and functions of proteins. While this introduction starting with DNA before getting to proteins seems a little roundabout, I wanted to start with something most people understand – DNA, and then extend it into something many people don’t – proteins. Scientists are also very interested in looking at polymers that are structurally similar to proteins. ‘Polymer’ is simply a more scientific way to refer to any compound like DNA – something that is made up of a linked series of repeated simple building blocks. In the case of DNA, the repeated simple building blocks (or monomers) are C, G, T, and A. In the case of proteins, there are 20 different amino acids. Back to the DNA-necklace analogy. Much like the ‘beads’ C, G, T, and A are strung on a very long necklace to make DNA, the 20 different amino acid ‘beads’ are strung along a long necklace to make a protein. Polymers are broadly useful in many applications, including drug-delivery, materials, electronic devices, and tissue engineering, so scientists are always looking for new polymers that have unique properties or structures.
Forgive the lengthy background, I’m trying to ease the non-scientific reader into a really interesting paper that was recently published in the journal Nature Materials. Titled “Free-floating ultrathin two-dimensional crystals from sequence-specific peptoid polymers,” this paper comes from Ron Zuckermann’s group at the Lawrence Berkeley National Laboratory in California. The Zuckermann group has long been investigating the structure and function of a type of polymer referred to as ‘peptoid’. These peptoid polymers are closely related to proteins in terms of the type of building blocks used. Proteins use 20 amino acids as their building blocks, which gives proteins a somewhat rigid ‘amide’ backbone. Peptoids share a similar type of ‘amide’ backbone with proteins but do not use the 20 amino acids as their building blocks. Peptoids instead use oligo-N-substituted glycines as their building blocks, so peptoids have tertiary amide backbones, rather than the secondary amide backbone typical of proteins. Apologies non-scientific readers, your understanding of the exact nature of peptoids vs proteins isn’t necessary to understand the coolness of this paper, but I included it for scientific completeness.
One big challenge many scientists have faced when making new materials is controlling the structure of the polymers. Proteins are ideally suited for folding in to very defined structures that can carry out pretty complex functions. Proteins include antibodies – molecules that tell our immune system when we’re under attack from viruses or bacteria, enzymes – molecules that carry out chemical reactions, and also help take the information stored in DNA and turn it into more proteins, messengers – molecules that transmit signals throughout our body, or structural components – molecules that support cells, and on a larger scale, allow the body to move. This is pretty hard to beat in the lab in terms of making a new type of polymer that can carry out such complex functions. This is largely due to the fact that it is difficult to predict what kind of structure (if any) a new polymer will have. It could just be a limp noodle that doesn’t do anything but stay as a linear molecule unable to perform any useful task. Or it could fold up in to a tangled mess disordered rats nest with no ability to perform.
In this new paper, the Zuckermann group very cleverly thought about what type of polymers they could make and predicted what types of structures these polymers could take on. They based their predictions about the potential structure of their polymers on two basic interactions – hydrophobic (water hating) and hydrophilic (water liking) interactions. These hydrophic and hydrophilic interactions are two types of interactions that make things either want to group together or get as far apart as possible. We see this type of thing every day in a bottle of salad dressing. There is an oil layer and a water layer – no matter how much we shake the salad bottle, the two things will mix briefly but then will quickly return to their separate portions of the bottle. Water molecules attract each other, as oil molecules attract each other. However, water and oil molecules repel each other. This is true for any type of hydrophic molecule (like the oil in salad dressing) or hydrophilic molecule (like the vinegar and water in salad dressing). The specific type of hydrophilic interaction that we care about for understanding this particular paper is between positively and negatively charged molecules.
Some trial and error was needed on the part of these scientist to find a polymer with optimal structural characteristics, but in the end they found something really cool. They could predictably and repeatedly form robust nano-materials with atomically defined structure. If that description doesn’t sound it, this is very difficult thing to do. They made 2-dimensional sheets that were 100 microns square and only 3 nanometers thick. Put into more understandable units, that means that this molecular sheet has a surface area that is over 3000 times the ‘thickness’ of the sheet. Kind of like a piece of paper – paper is 8.5 by 13 inches, giving it a surface area of 110 inches. One piece of paper is about 0.004 inches thick, meaning the surface area of a piece of paper is 27,500 times the ‘thickness’ of a piece of paper.
How did they do this? While this may not be the exact order of events that happen on a molecular scale, here’s how to understand the formation of these nano-sheets. The scientific group researching this issue made two kinds of peptoid polymers. We can think of both of these types of peptoid polymers as long pieces of ribbon. One of the long sides of the ribbon was hydrophic (water hating), while the other long side of the ribbon was hydrophilic (water loving). Now remember, there are two types of ribbon. Both have one long hydrophic side. The two ribbons differ in their hydrophilic long side. One type of ribbon is essentially positively charged, while the other type of ribbon has a negatively charged hydrophilic side. Much like opposite poles of a magnet are drawn to each other, the negatively and positively charged ribbons are drawn together to form a 2 dimensional sheet. Once formed, this sheet has a hydrophilic side (made from all of the negatively and positively charged sides of the ribbon aligning) while the other side of the sheet is hydrophibic. Two of these sheets them come together, forming a simple sandwich where the hydrophilic sides are on the inside of the sandwich and the hydrophobic sides are on the outside of the sandwich. This simple structure does not accurately reflect the difficulty science has had with forming such well-defined molecular structures. In fact, this is the first example where scientists use the type of information found in proteins (the 20 amino acids) and translated this information into a non-natural polymer. Peptoids are not found in nature, so this nano-material is entirely synthetic. The authors propose that this research could lead to a whole new class of artificial materials that can precisely form specific structures. This simple ultra-thin sandwich-y material could be further elaborated for lots of different scientific applications, such as new sensors or membranes, or could serve as a scaffold for building electronic devices, materials for drug delivery, or tissue engineering. Pretty amazing what a little sheet could accomplish.