Tiny structures made of mechanically interlocked molecules can act as "molecular machines," and this hugely exciting area of chemistry research that stretches back decades has seen some particularly significant developments in recent years. Princeton University researchers have produced yet another one by using self-assembling peptides to form the world's tiniest interlocked biomechanical structures, which measure just one billionth of a meter in size.
The origins of molecular machinery can be traced back to the early work of France's Jean-Pierre Sauvage, who was working in the field of photochemistry in 1983 and discovered a pair of molecules linked around a copper ion. When the copper was removed, it left the molecules connected via mechanical linkage, rather than a typical covalent bond powered by the sharing of electrons between atoms. This structure laid the groundwork for fellow researcher Fraser Stoddart to thread a molecular ring onto a molecular axle in 1991, and then Ben Feringa to develop the first molecular motor in 1999.
Sauvage, Stoddart and Feringa were awarded the 2016 Nobel Prize for Chemistry for their pioneering research on molecular machinery, and their work continues to inspire others in the field. In the last decade, we've seen the creation of the world's first artificial molecular pump designed to transfer energy between molecules, advances made toward molecular machines that walk with leg-like structures to treat disease, and molecular nanosubmarines that kill off specific cancer cells. Beyond the realm of the human body, molecular machinery also has promise in energy storage, and the development of new materials and sensors.
Most of the mechanically interlocked molecules that form the basis of these molecular machines have so far relied on metal ions and harsh solvents to form the desired structure. Princeton University scientists set out to sidestep the need for artificial building blocks by synthesizing mechanically interlocked molecules entirely from natural biomolecules, in this case the tiny strands of amino acids known as peptides.
The team used a naturally occurring lasso-shaped peptide called microcin J25 as their starting point. The amino acids making up this peptide were genetically engineered to perform an entirely different role, and self-assemble into very different shapes when placed in water. These included two interlocked rings, a ring on a dumbbell, a daisy chain and an interlocked double lasso. All measured one billionth of a meter in size.
"We've been able to build a bunch of structures that no one's been able to build before," says A. James Link, professor of chemical and biological engineering and the study's principal investigator. "These are the smallest threaded or interlocking structures you can make out of peptides."
Interestingly, some of these structures were able to toggle between two or more different shapes, which the researchers say lays the foundations for a kind of "biomolecular switch." More broadly, the work demonstrates the formation of highly complex structures and could open the door to sophisticated new biomolecules for use in everything from material design to medical care.
"It's really building a bridge between the biological world, and what until now has been the playground of synthetic chemistry," says Link.
The research was published in the journal Nature Chemistry.
Source: Princeton University
