@article {19946, title = {Out of equilibrium assembly of carbohydrate amphiphiles as a modulator of the supramolecular helicity and gelation}, journal = {FoReCast 2nd Workshop}, year = {2019}, month = {2019-07-11 00:00:00}, address = {Porto-Portugal}, abstract = {

Altered glycosylation is a hallmark of almost any cancer. As a result, cancer cells communicate differently with their environment: supramolecular interactions between carbohydrates expressed on the cell surface and the aromatic amino acids from the surrounding proteins (e.g. enzymes, receptors) are the ones that govern the glycan recognition and the following cell response. In this work, we studied the impact of carbohydrates stereochemistry and energy input (accelerated metabolism in cancer cells is responsible for their high energy) affect CH-p interactions determining the glycan recognition.1

We synthesized three carbohydrate amphiphiles that have the same aromatic portion (fluorenylmethoxycarbonyl (Fmoc)) but differ by their carbohydrate unit: the stereoisomers glucosamine (GlcN), galactosamine (GalN) and mannosamine (ManN). The carbohydrate amphiphiles were suspended in water, heated to 75-80{\textdegree}C until complete solubilization and then cooled at different rates. Fmoc-ManN was insoluble at these conditions.

Fluorescence spectroscopy confirmed that supramolecular interactions occur upon cooling (450-480 nm region). Atomic force microscopy and scanning electron microscopy revealed that these interactions result in formation of nanofibers that form hydrogels. Circular dichroism spectroscopy (CD) showed that the supramolecular helicity is dependent on the cooling rate (i.e. fast -40{\textdegree}C/min or slow -5{\textdegree}C/min cooling) and on the carbohydrate stereochemistry: a positive signal was observed for both amphiphiles when fast cooling rate was used and the slow cooling rate resulted in an inversion of the signal for Fmoc-GalN. The nucleation and growing of the fibres was also influenced by the carbohydrate stereochemistry: Fmoc-GalN nucleation process is slow (long fibres) and Fmoc-GlcN nucleation process is fast (more but shorter fibres). All these differences affected the properties of the formed gels as confirmed by confocal imaging. Viscoelastic properties were also different, i.e. the storage modulus G{\textquoteright} for the obtained gels. We observe that Fmoc-GlcN hydrogels have higher storage modulus than the Fmoc-GalN ones and it is also higher for the gels obtained at slow cooling than for ones generated at fast cooling. In all the cases the sol-gel transition occurs between 35-55{\textdegree}C.

In conclusion, we observed that, in biological systems, carbohydrates can code and transfer information not only as a function of their stereochemistry but also as a function of the energy input/cooling rate.

}, keywords = {carbohydrates, self-assembling, supramolecular helicity}, author = {Castro, V. I. B. and Gao, Y. and Brito, A. and Soares da Costa, D. and Chen, J. and Ulijn, R. V. and Reis, R. L. and Pashkuleva, I. and Pires, R. A.} }