The language of cellular activity is written in glycans.
A glycan is a biological compound built of specifically constructed sugar molecules. Proteins fabricate glycans and wear them as utility clothes as well as using glycans as cellular construction materials.
Glycans and glycoproteins are the stuff cells walls and membranes are made of. To get the desired stiffness in constructing cellulose, plants use sugars built to withstand the rigors of rainfall and wind.
Nucleic acids – DNA and RNA – are made up of just 4 nucleotide letters, arranged into words that comprise the language called genetics. Glycans have an alphabet of hundreds of simple monosaccharides which can be strung together into a vast array of polysaccharide sequences and structures.
The combinatorial potential of glycans is uniquely intricate. Glycans are the only nonlinear biopolymer, with multifold branching potential per sequence.
The molecular structure of glycans form a language. “Languages are actually quite similar to molecular sequences: the order of the elements matters, elements that are not next to each other can still influence each other, and their structures evolve over time,” observed biologist Rani Powers.
Moreover, glycans are malleable. Enzymes recompose glycans at will. Thus glycans act as a communication medium as well as a structural material. “Glycans display great phenotypic variability. Sequences can be changed depending on environmental conditions, such as the level of extracellular metabolites, facilitating rapid responses to changes,” noted biologist Daniel Bojar.
Glycans serve as protein communiques and assembly guides. “The glycosylation of proteins is a major protein modification that extensively occurs. Glycans play key roles in protein quality control and in the specific modifications leading to mature glycoproteins,” wrote biochemist Łukasz F. Sobala. “Sugar molecules provide instructions for proteins to fold into their correct 3D structure as well as transport instructions for the protein to be brought to its next destination within the cell. Glycosylation is facilitated by various enzymes that synthesize, trim, check and modify these sugar molecules,” explained Australian biochemist Spencer J. Williams.
How proteins know how to make the glycans they do is a mystery. DNA artifactually encodes for bioproducts related to fabricating proteins and the amino acid tools that proteins use – but not glycans. Glycans derive from a 2nd-order formula for which the source of the blueprints is unknown. Glycans seem to spring from the minds of proteins, which apparently innately know how to build and manipulate glycans.
Because glycans comprise the outermost layer of all living cells, they are necessarily involved in the processes of cell interaction and pathogenic infection. Viruses and bacteria interface their glycan-coated fingers with glycans on cell membranes to suss the best point for slipping into a host cell.
“The glycans most associated with infection bear a striking resemblance to glycans found on the cells that form the mucosal barriers in animals’ bodies, which keep pathogens out,” said computational biologist Diogo Camacho. “This suggests that the glycans on pathogenic bacteria evolved to mimic those found on the hosts’ cells, facilitating their entry and evasion of the immune system.”
Immune system cells read glycan signage on other cells to determine their status and integrity. Infection typically leaves telltale signs on cell membranes, though some especially savvy viruses try to cover their tracks.
The building blocks of glycans are monosaccharides: the simple sugars composed of only carbon, hydrogen, and oxygen. These 3 elements are both abundant and brimming with readily manipulable energy and material potentials. From the simplest of biological substances the empires of life are built.
Daniel Bojar et al, “Deep-learning resources for studying glycan-mediated host-microbe interactions,” Cell Host & Microbe (28 October 2020).
Lindsay Brownell, “Learning the language of sugars,” Wyss Institute (28 October 2020).
Lukasz F. Sobala et al, “Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target,” PNAS (5 November 2020).
“Sugar-coated viral proteins hijack and hitch a ride out of cells,” ScienceDaily (6 November 2020).