What we couldn’t measure before: the stickiness of molecules

When building with molecules, it is important to understand how they stick together when, amongst others,  designing capsules for transportation of medication in the body. After all, how can you construct a car if you don’t know how the components work? Researchers of the TU Eindhoven enable us to measure how long it takes for small molecules (monomers) to break free from a larger molecular complex (polymer), without influencing the movement of the polymers. Today, biomedical engineer René Lafleur, dr. Xianwen Lou, professor Bert Meijer and colleagues published a paper about this research in Nature Communications.

The movements of molecules is often measured by connecting a coloring to the molecule. However, the coloring is large in size in relation to the molecule, therefore influencing the movement. PhD candidate Lafleur now proved, together with colleague Xianwen Lou, that the technique used for studying the folding of proteins (also a type of polymer), ‘hydrogen/deuterium exchange mass spectrometry (HDX-MS)’, can also be used for studying supramolecular polymers.

Building with molecules

A car mechanic needs to have knowledge of the parts before he can construct a car. The same thing holds for ‘building’ with molecules; for example making capsules to transport medication in the human body or making a medical hydrogel for local release of medication and stem cell therapy.

These types of capsules or materials are often made from polymers; these polymers are built from smaller building blocks, so-called monomers. With self-assembling molecules, these monomers automatically form polymers, for example in the shape of long wires or small spheres in which medication can be transported.

In these self-assembling, supramolecular polymers, the monomers are not attached to each other but they lightly stick together. This enables the monomers to leave the polymer and return to it. The ambient temperature or pH influences this flexibility (how easily they go in and out of the polymer). This dependence on temperature or pH is, amongst others, important when researchers or manufacturers want to apply the capsules in the human body, where pH and temperature tend to differ per location.

Movement 'in view'

So how does it work? After the in water dissolved monomers stuck together to form a polymer, the researchers dissolve the polymers in heavy water. The monomers that leave the polymer will be exposed to the deuterium in the heavy water, resulting in the replacement of the hydrogen atom by a deuterium atom that is just a bit heavier.

The small change in the mass is detected by Lou and Lafleur and is also measureable when the monomer has retaken its place in the polymer. The speed with which the monomers increase their mass is therefore a measure for the speed with which the monomers leave the polymer.

Interestingly enough, the research results show that many monomers already leave the polymer within minutes and therefore gain mass, however others take hours or days. Furthermore, the researchers have shown that a small change in the size of the monomer has an influence on the movements. Larger monomers will remain in the polymer longer and take more time to start moving as compared to smaller monomers. These differences were not measureable before, because the coloring molecules were too large; with the HDX-MS technique, even the influence of small differences in molecular size on the movements of the molecules can now be measured.

Reference

Xianwen Lou et al., Dynamic diversity of synthetic supramolecular polymers in water as revealed by hydrogen/deuterium exchange, Nature Communications (15 May 2017).
DOI: 10.1038/NCOMMS15420.

René Lafleur

René Lafleur attended the Eindhoven University of Technology, and earned his BSc in Biomedical Engineering with honors. During his Master program, he performed an internship at the California Institute of Technology (Caltech) with Prof. Dr. David A. Tirrell. At Caltech, he developed artificial extracellular matrix proteins to create hydrogels. During his graduation research in Prof. Dr. Bert Meijer’s group, he focused on the synthesis of supramolecular building blocks containing enzymes. After receiving his Master’s degree, he started his doctoral research under the supervision of Meijer, and became fascinated by the kinetics of supramolecular polymers.

Dr. Xianwen Lou

Xianwen Lou obtained his M.Sc. in Analytical Chemistry from Dalian Institute of Chemical Physics, Chinese Academy of Science in 1988 under the supervision of Prof. L. Zhou, and his Ph. D. degree from Eindhoven University of Technology in 1997 under the supervision of Prof. Dr. C.A. Cramers and Dr. H.-G. Janssen. In 1998, he worked as a postdoctoral fellow in the Energy and Environmental Research Center at the University of North Dakota with Dr. S.B. Hawthorne. In 1999, he returned to Eindhoven University of Technology and started working in the group of Prof. Dr. Meijer.

Prof. Dr. Bert Meijer

Bert Meijer is Distinguished University Professor in the Molecular Sciences, Professor of Organic Chemistry at the Eindhoven University of Technology and scientific director of the Institute for Complex Molecular Systems. After receiving his PhD degree at the University of Groningen, he worked for 10 years in industry (Philips and DSM). In 1991 he was appointed in Eindhoven, where he supervised over 85 PhD students. In the meantime he has part-time positions in Nijmegen and Santa Barbara, CA. Bert Meijer is a member of many editorial advisory boards, including Advanced Materials, Angewandte Chemie, and the Journal of the American Chemical Society. Bert Meijer has received a number of awards, including the Spinoza Award in 2001, the ACS Award for Polymer Chemistry in 2006, the AkzoNobel Science Award 2010, the Cope Scholar Award of the ACS in 2012, the Prelog medal in 2014 and the Nagoya medal in 2017. He is a member of a number of academies and societies, including the Royal Netherlands Academy of Science, where he is appointed to Academy Professor in 2014.