DNA repair enzyme failure triggers inflammation and accelerates aging in cells

Techniques are always evolving and the areas that they are going to be used in are going to be virtually unlimited. Petrochemistry, for example, is just one area, although that is the area of this particular talk. They are just as useful in environmental analysis, food and beverage analysis, fragrance, forensic science. It cuts across all these areas, so the research involving ionic liquids, or using them, can go in any direction.

Stupp and his team posited that "dancing molecules" might encourage the stubborn tissue to regenerate. Previously invented in Stupp's laboratory, dancing molecules are assemblies that form synthetic nanofibers comprising tens to hundreds of thousands of molecules with potent signals for cells. By tuning their collective motions through their chemical structure, Stupp discovered the moving molecules could rapidly find and properly engage with cellular receptors, which also are in constant motion and extremely crowded on cell membranes. Once inside the body, the nanofibers mimic the extracellular matrix of the surrounding tissue. By matching the matrix's structure, mimicking the motion of biological molecules and incorporating bioactive signals for the receptors, the synthetic materials are able to communicate with cells. "Cellular receptors constantly move around," Stupp said. "By making our molecules move, 'dance' or even leap temporarily out of these structures, known as supramolecular polymers, they are able to connect more effectively with receptors."

Affimers can be combined with traditional biological tests to increase our understanding of proteins. For example, affimers have been used in affinity assays, among others. They have also been used in biosensors and in cell cultures to manipulate cell signaling. Affimers have been successfully applied both in vitro and in vivo. Some of the applications that have been tested using affimers include cell imaging, super resolution microscopy, protein function modulation, magnetic nanoparticle formation, and MRI reagent development. Affimers with enhanced specificity for tubulin have been used in super resolution microscopy with high success, and can target regions of the tubulin structure that antibodies are typically restricted from. It is likely that more applications will be discovered in the future as the use of affimers becomes more widespread. For example, thanks to growing libraries of affimers, it has been possible to create affinity microarrays to discover biomarkers and potential pharmaceuticals. By finding biomarkers, affimers have been applied to cancer studies, where they have been used to target a protein in tumor vessel formation called the VEGF receptor.

The pKa for an amino acid is an acid dissociation constant that refers to the equilibrium between the protonated and deprotonated forms of the backbone amino group, backbone carboxyl group, and any potential acid/base component of the variable group. The net charge of the protein is determined by summing the charge of individual amino acids across the protein. pKa relates to the equilibrium constant and defines the transition between two structural forms of an amino acid–protonated and deprotonated. Amino acids possess distinct pKas for the carbonyl group, amino group, and any functional groups on the side chain that may be protonated or deprotonated. There is always one more structure than the number of pKa values for amino acids. For example, if there were two pKa values, three structures can be discerned. This is illustrated below using glycine, which has two pKa values – pKa 1 represents the (de)protonation of the carboxyl group and pKa2 represents the (de)protonation of the amine group: When the pH< pKa protonation of the amino and carboxyl groups occurs, resulting in a net +1 positive charge for glycine. When the pH is increased to a value between the two pKas(pKa2>pH> pKa1), the carboxyl group is deprotonated while the amino group remains protonated. This represents the zwitterionic form of the amino acid as it simultaneously possesses a positive and negative charge. When the pH> pKa2, the amino group is deprotonated and loses its charge. The amino acid now carries a net negative charge of -1. The zwitterionic form of the amino acid can exist at any pH value between pKa1 and pKa2.

At its core, pain involves sensory neurons that extend axons from their cell bodies into peripheral tissues and the spinal cord. Understanding these sensory terminals, especially their responses under various conditions such as inflammation, is pivotal. Our Axon-RNA-centric approach allows us to detect RNA changes and leverage them to alter sensitized states, providing a more accessible avenue for drug targeting.