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Posted on 6 July 2022 by Hanna Kurlanda-Witek

Insights Into Supramolecular Chemistry and Nanoscale Imaging

Jean-Marie Lehn, 1987 Nobel Laureate in Chemistry, at #LINO22

Supramolecular chemistry is the type of chemistry that isn’t governed by covalent bonds − when atoms share at least one pair of electrons. Instead, atoms are held together by weak and reversible bonds, such as van der Waals forces, metal-ligand bonds, or halogen bonds.

Mastering the Non-Covalent Bond

Jean-Marie Lehn won the Nobel Prize in Chemistry in 1987 for developing cryptands−spheroidal compounds built from six oxygen and four nitrogen atoms, which very selectively bind various metal ions. Over time, Lehn’s research in supramolecular chemistry gravitated towards self-organization processes, or “the use of molecular recognition to control and direct the spontaneous formation” of complex molecules.

“Supramolecular chemistry is a dynamic chemistry,” said Lehn during his lecture. Because of their tunable and reversible properties, supramolecular materials don’t behave like conventional materials; they can even resemble biological materials. It is also an ever-widening field, with applications in materials science, life sciences, medical devices and drug discovery.

One example are supramolecular polymers, which can be used as implants in the circulatory system; new tissue grows in and around the implant, after which it biodegrades, minimising the risk of complications from the body rejecting foreign materials.

Galaxies Within Cells

“Chemistry must become the astronomy of the molecular world,” said Alfred Werner, a Swiss chemist and Nobel Prize Laureate in Chemistry in 1913. Advancing technology enables us to better see this molecular world, even at the nanoscale, and to fully appreciate the amazing complexity of what’s going on inside a human cell.

William E. Moerner developed single-molecule microscopy, which localises single molecules with high precision. The ability to detect single molecules absorbing light in condensed matter was discovered in 1989, and the blinking and switching of single green fluorescent protein at room temperature was determined in 1997. These two elements led to super-resolution imaging, using single-molecule active control microscopy (SMACM), one of several super resolution microscopy techniques.

Moerner
William Moerner during his lecture

Recently, Moerner’s research group worked to visualise the genomic RNA (gRNA) and double-stranded RNA  (dsRNA) of a human coronavirus using multi-colour super-resolution.

The spatial organisation of the genetic material within the cell is particularly eye-catching (the gRNA look like galaxies!). But the images also convey important information on viral infections, such as where exactly are the gRNA and dsRNA localized in relation to one another. Also, the density and size of gRNA clusters appear to grow with the duration of the infection.

“Two revolutions in spatial resolution have transformed cellular imaging, super-resolution optical microscopy and cryogenic electron microscopy,” said Moerner. “The strengths of super-resolution are in fact the weaknesses of electron microscopy and vice-versa (…); electron tomography does show you high resolution but it shows you a grayscale image. On the other hand, the single molecule images tell you the precise location of individual molecules with specificity, so the imaging from the light microscopy is highly specific.”

By combining super-resolution fluorescence microscopy and cryogenic electron tomography, it’s possible to see incredible detail in the cell, including the localization of particular proteins. The good news is that what we can observe under the microscope will only get better as new techniques are further refined and developed, leading to a greater understanding of the galaxies inside cells.

Hanna Kurlanda-Witek

Hanna Kurlanda-Witek is a science writer and environmental consultant, based in Warsaw, Poland. She has a PhD in geosciences from the University of Edinburgh, where she spent a lot of time in the lab. As someone familiar with both worlds of research and industry, she enjoys simplifying science communication across the divide.