Aminocelluloses that reversibly assemble into tetramers could form a new class of biosensors

Researchers have used ultracentrifugation to show that some carbohydrates behave like proteins, sticking together in complex, well-ordered arrangements that readily dissolve and reform in response to concentration changes.1

One would normally expect carbohydrate molecules to either float around independently like the sugar in your tea, or to form large macromolecular aggregates like cellulose fibres that are hard to dissolve. Until recently there was no hint of the complex yet regular self-assembling architecture observed in proteins such as haemoglobin.

A few years ago, however, the groups of Thomas Heinze at the Friedrich Schiller University of Jena, Germany, and Stephen Harding at the University of Nottingham, UK, reported that soluble carbohydrates derived from chemically modified cellulose can assemble to form oligomers consisting of up to four molecules. They determined the masses of the assemblies by measuring their sedimentation speed in the analytical ultracentrifuge, a classical method of protein assembly studies. When they reduced the carbohydrate concentration, they found that some but not all of the monomers could be retrieved.2

In their latest study, the two groups identify one specific kind of modified carbohydrate, aminocellulose derivative AEA-1, which can assemble into tetramers in a fully reversible fashion. For a precise measurement of the molecular mass of the assembly, the group used the analysis of the equilibrium between sedimentation and (upward) diffusion in the centrifuge, as a function of the molecular concentration. They found that the molecules that form tetramers at high concentrations can readily return to the monomeric state when they are diluted. Moreover, the research also showed that the tetramers can further assemble into higher order aggregates, similar to the case of the sickle-cell variant of haemoglobin.


Researchers showed that the aminocellulose derivative AEA-1 can reversibly self-assemble into tetramers

‘We couldn’t believe our eyes when we first saw the ultracentrifuge profiles, but it checks out,’ says Harding. ‘In my years of working on polysaccharides and other types of carbohydrate polymer with this method I have never seen anything like it.’

Helmut Cölfen from the University of Konstanz, Germany, welcomed the discovery, saying: ‘How a polysaccharide, which has a considerable distribution of molecule lengths, can behave like a protein, with a defined and unique molecular mass forming defined aggregates, is not yet known. Finding out what kind of interaction can lead to this remarkable self-association behaviour can be the key for the design of polysaccharides with entirely new functions.’

Heinze’s group plan to develop chemical synthesis approaches to create well-defined monomers that still show the same assembly behaviour. They also hope that their ‘protein-like’ aminocellulose materials, accessible from the abundant and renewable resource cellulose, may find applications in the biosensors field. ‘A new class of biosensors with a very good detection limit may be developed because the proteins, peptides, and antibodies lose almost no activity in this protein-friendly environment of aminocellulose due to the non-covalent interactions,’ Heinze explains. Rob Field from the John Innes Centre at Norwich, UK, shares his optimism. ‘If the assembly principles for polysaccharide architectures can be understood and harnessed, this could open the way for a whole new era of sustainable and biocompatible materials.’