Targeting Cancer Cells with Self-Assembling Molecular Cages

Taking inspiration from nature, chemists have developed a new method to destroy bone cancer cells that utilizes artificial extracellular matrices.

Because extracellular matrices provide support and structure to the cells making up many organs and tissues, their artificial production has been very appealing to tissue engineers. Scientists searching for a method to produce them in the lab have mainly focused on self-assembling peptides.

Cancer cells before (left) and after (right) 7 hours of exposure to self-assembling
carbohydrate molecules.

Credit: J. Am. Chem. Soc.

In order to exploit one of the common features of bone cancer cells, Bing Xu of Brandeis University designed such a peptide with one important modification; it is only capable of self-assembly upon removal of a phosphate group. Once it’s gone, the molecules have a hydrophobic and a hydrophilic end, allowing them to aggregate into films like the lipids that form membranes in the body.

This property made them perfect for targeted destruction of certain types of cancer cells, which produce alkaline phosphatase, an enzyme that removes phosphate, in far greater quantities than healthy cells do.

Another researcher, Rein V. Ulijn of the City University of New York’s Hunter College, took it a step further. Because carbohydrates can produce such a rich diversity of structures, he endeavored to use them in a similar way. 

To create a carbohydrate molecule that would self-aggregate, he attached a hydrophilic glucosamine to a hydrophobic aromatic. Then he added a phosphate group that would interfere with the molecules’ mutual attraction to its peers, thereby postponing the formation of a film until the group was cleaved off, hopefully, near a phosphatase-rich cancer cell.

Subsequent tests investigating the effectiveness of the substance against cancer cells yielded optimistic results. The chemical killed 95% of cultured bone cancer cells, while only 15% of healthy control cells perished after 7 hours of exposure. 

Written by: Aisling Williams

Source

Berg, Erika G. "Self-Assembling Carbohydrates Trap Cancer Cells In A Cage." Chemical & Engineering News (2015): n. pag. 20 Jan. 2015. Web. 27 Jan. 2015.

Crystal Nucleation More Nuanced Than Once Thought

The formation of crystals is paramount to the production of an enormous variety of products we use every day. From things as simple as sugar or salt to revolutionary technology involving crystalline metals and silicon, the understanding of the processes of crystal growth has been a staple of scientific progress. However, recent research indicates that nucleation – the process initiating the growth of a crystal – may be much more complex than previously imagined.

The classical model of crystal growth breaks the process down into two major steps. First, ions or molecules come together into a tiny crystalline seed, on whose structure the properties of the emerging crystal will depend. From that point, other solvated ions fall into place, thereby expanding the lattice and growing the crystal. As the crystal grows, the bulk free energy of the mass decreases; yet at the same time, the solid-liquid interface expands, increasing free energy. Nucleation is officially defined as the point at which the crystal reaches the critical size threshold beyond which the energy benefit of growth exceeds the cost.

However, this model is proving to be inadequate in the face of mounting evidence. There seem to be a variety of different mechanisms from which a crystal structure can emerge. For instance, research done in 2002 at MIT involved inducing crystallization in glycine using laser pulses. By altering the polarization of the incident laser, the group produced a variety of different crystal polymorphs. 

According to MIT Chemical Engineering professor Allan S. Myerson, such a phenomenon indicated that the laser must have been acting on some pre-existing structure that was somewhere in between an ordered crystal and completely solvated molecules.

A more recent study in 2014 visually examined the microscopic behavior of calcium carbonate as it formed crystals. Calcium carbonate represented an interesting substance for such a study due to its tendency to form a wide variety of crystal polymorphs, including calcite, aragonite, and vaterite. While material often appeared to nucleate into any of the three directly, sometimes the molecules would aggregate into unstructured blobs which then transformed into aragonite or vaterite. 

This sort of behavior may be important beyond the formation of the initial crystal ‘seedling’, as it is possible for actual crystal growth to depend on the formation of such viscous blobs. Perhaps individual ions or molecules are incapable of adding to the growing crystal in isolation, and need to first form groups to proceed.

The behavior of real systems appears to be extremely diverse. In the words of James J. De Yoreo, who lead the calcium carbonate study, “Think up any mechanism or pathway you want, and there will probably be some system that behaves that way.”

Written by: Aisling M Williams

Sources

Kemsley, Jyllian. "Illuminating Crystal Nucleation." Chemical & Engineering News93.2 (2015): 28-29. CEN RSS. Chemical & Engineering News, 12 Jan. 2015. Web. 13 Jan. 2015.