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.

6th Annual Science Carnival

On November 1^st, the 6^th annual CSUCI-hosted Science Carnival proved once more to be a roaring success.

Being entirely volunteer-run, the carnival remains free to attend and continues to attract guests of all ages. Students between Kindergarten and 8^th grade, many with siblings and parents in tow, flocked to Thurgood-Marshall elementary school to participate in the festivities.

From Biology and Chemistry to Paleontology and Physics, the carnival provided over 70 dazzling science demonstrations and activities to fascinate and inspire a younger generation.

Students admire a demonstration of UV fluorescent chemicals.

Fire isn't always yellow! This volunteer shows a crowd how the color of a flame
can actually depend on what compound is undergoing combustion.

The high-frequency electromagnetism associated with the plasma filaments in a
plasma lamp can induce a nearby fluorescent lightbulb to light up!

This ball python was one of many animals present at the science carnival.

Angular momentum is a physical phenomenon so rarely encountered that even
adults found this demonstration strange and fascinating.

This ping pong ball cannon made it clear
just how powerful air pressure can be.

This apparatus pumps air in and out of a pair of real lungs!

Many guests were surprised by the rich topography
of the microsocopic world.

Live crabs, starfish and many other marine creatures
made this booth particularly popular.

Unprecedented Control Over Organic Synthesis Using Modified Enzymes

Drawing inspiration from the world of biology, researchers have developed a novel approach to solving a long-standing problem in organic synthesis – regioselectivity.

The vast majority of drugs contain nitrogen, driving chemists to search for more efficient and selective methods to form new C-N bonds in substrate hydrocarbons. However, one of the most stubborn obstacles in the way of creating the desired compound is regioselectivity – the preference of a reaction to make or break bonds at particular sites of the substrate molecule over others.

This troublesome habit of nature often makes it very cumbersome to come up with a reaction mechanism that produces a desired molecular structure, at least with anything like a reasonable yield. The traditional approach would be to focus on the substrate molecule, modifying it in such a way as to make some particular carbon more likely to be that which forms the bond. Sometimes this means coming up with weird, exotic molecules that may be expensive or otherwise difficult to obtain.

Rather than manipulating the substrate, it would be much more desirable to have selectivity be determined by the catalyst. This way a chemist could produce different products from the same starting material simply by modifying the catalyst of the reaction.

Regioselectivity is determined by the enzyme catalyst.

Researchers at California Institute of Technology have come up with a way to accomplish just that. By engineering a natural biological enzyme, the team created two artificial variants which steer nitrogen atom transfer of a particular reaction in complementary directions. One enzyme favors ring-closing amination at the α-position of an alkyl substituent on a benzene sulfonyl azide. The other enzyme favors amination at the β-position. Simply by changing the catalyst, they have been able to switch the reaction to favor one product over the other by over 95%.

Synthetic biology may still seem like it belongs in the realm of science fiction to many, but the degree to which these enzymes have controlled the outcome of the reaction is difficult to ignore.

Considering the trouble these types of reactions have given scientists in the past, it may be reasonable to expect these new methods to gain favor in the future. The modification of enzymes for use in organic synthesis, according to the researchers, represents a promising platform for solving long-standing selectivity problems.

Source

Hyster, Todd K., Christopher C. Farwell, Andrew R. Buller, John A. McIntosh, and Frances H. Arnold. "Enzyme-Controlled Nitrogen-Atom Transfer Enables Regiodivergent C–H Amination." Journal of the American Chemical Society. N.p., 5 Nov. 2014. Web. 09 Nov. 2014, 136 (44), pp 15505–15508

Breaking Biofilms with Simple Compounds – A Novel Approach to Fighting Bacteria

The vast majority of chronic bacterial infections involve the formation of biofilms. On their own, individual bacteria tend not to represent much of a threat when met with the average human’s immune arsenal. 

However, some types of bacteria have developed a particularly effective defensive strategy.  By grouping together into slimy aggregate colonies, otherwise known as biofilms, bacteria can make themselves virtually impervious to destruction through conventional means. Once a biofilm forms, an infection may become chronic, or even fatal.

Luckily for us, researchers at the University of Washington, Seattle have developed a new method to turn bacteria’s best defensive strategy against them.

Credit: ACS Sustainable Chem. Eng.

In order to form a biofilm, bacteria secrete polysaccerides and proteins which in turn form an extracellular matrix. As a consequence, their external environment becomes unusually saturated with dissolved salts and sugar, resulting in increased osmotic pressure on the cells. In order to compensate, bacteria fill their internal cytoplasm with small molecules called, unsurprisingly, osmoprotectants.

Researchers have focused their attention on these osmoprotectants. By synthesizing artificial analogs in the lab, they have been able to investigate various compounds that might interfere with their effectiveness. Ethylcoline appeared to be the most promising. It reduced biomass by 70%, and was the only compound tested that produced substantial effects without inhibiting bacterial growth.

Strange as it may seem, the fact that this approach doesn’t directly kill the bacteria is actually what makes it so appealing. By leaving the cells alive, selective pressure is minimized, making it incredibly difficult for the bacteria to adapt. 

Source

Madhusoodanan, J. (2014). Simple Molecules Block Bacterial Biofilms | Chemical & Engineering News. [online] Cen.acs.org. Available at: http://cen.acs.org/articles/92/web/2014/10/Simple-Molecules-Block-Bacterial-Biofilms.html [Accessed 15 Oct. 2014].

Most Complex Molecular Shape “Star of David Molecule” Finally Created in Lab

Over a quarter of a century’s worth of effort has finally come to fruition at the University of Manchester. Affectionately known as the ‘Star of David Molecule’, the beautiful interwoven threads of atoms represent a physical feat that scientists only years ago may have dismissed as impossible.

Image Credit: University of Manchester

The prospect of manually finessing strings of atoms around one another into such a precise configuration seems, even now, like the stuff of science fiction. And yet despite the odds, PhD student Alex Stephans has managed to create the beautiful interlocking molecule, and he did it by taking advantage of a quirk of chemical physics that the microscopic world of biology has known about for billions of years. 

The trick to creating such delicate molecular structures, it turns out, is to allow them to do it themselves. Instead of trying to wrap the interlocking triangles around one another manually, as chemists of the past have tried (and utterly failed) to do, Stephans took advantage of a process known to biologists as self-assembly.

“Nature does the same thing to assemble DNA,” said David Leigh, lead researcher and professor of Chemistry.  "Most have tried to take linear molecules and twist them around each other, but we choose our building blocks very care

fully."

The atoms involved were carefully chosen for their affinities for one another, so that the tiny interlocking triangles would fall into place as the molecule formed, driven by the same subatomic forces that had made such a structure virtually impossible in the past.

Although it may superficially seem like nothing more than a trivial exercise in scientific peacocking, the molecule may have some far-reaching implications. “When you look at viruses, some of their shells have these coatings made of a sort of chainmail of protein, and it's very tough but very light," says Leigh. "So the thinking is that if you could do the same thing with a man-made molecule, you could get those same benefits."

The research team hopes to use the self-assembly method to create even more complex molecules that might someday be used in what they call “molecular chainmail”. A material made out of such structures would be extremely lightweight, flexible, and incredibly strong.

By Aisling M Williams

Works Cited

Feltman, Rachel. "Scientists Create a ‘Star of David’ Molecule — a Step towards Molecular Chainmail." Washington Post. The Washington Post, 22 Sept. 2014. Web. 28 Sept. 2014.

Bondbreaker – New Game Plays from a Proton’s Point of View

Have you ever found yourself daydreaming about what life might be like from the point of view of a black hole, a particle travelling at the speed of light, or a proton?  Most inquisitive minds will grapple with such ideas at some point in their lives. The problem is that many scientific concepts are so far removed from our normal daily experience that it becomes nearly impossible to visualize them in a useful way. Physics simply doesn’t operate the same way at very small, very large, or very fast frames of reference, and the human mind learns its intuition through direct experience.

This is precisely the issue that indie game developer Andy Hall endeavors to address. After working for years in scientific outreach at the Museum of Science in Boston, Andy founded an independent game studio focused on science education called TestTubeGames. His most recently released project, BondBreaker, puts the player in control of a single proton. The game was designed to give the player a first-hand experience of the atomic-scale world, and through gameplay to develop an intuitive understanding of the real life forces at work there.

Through learning to operate in the strange environment, players complete tasks such as capturing electrons, forming bonds with other atoms to become molecules, absorbing photons and releasing them again, and in so doing advance through the levels. “You start this game in the smallest way possible - as a single proton. You don’t even have an atom to call your own. Learn what it takes to be a proton, experience subatomic forces, and with luck and determination, grow into an atom of your own. Collide atoms together into molecules, or break them apart again using lasers, tunneling microscopes, and heat.”

By the end of the game, the player should have gained an intuitive understanding of a multitude of atom-scale physical concepts, including  “Atomic Energy Levels, Light Absorption, Muons, and their crazy effect on atoms, Morse Potentials, Plasmonics: a way to focus light more precisely than a laser, and way more.”

Hall created BondBreaker in a collaborative effort with physicists at UC Irvine’s CaSTLE (Chemistry at the Space Time Limit) research center. There, scientists are investigating small-scale physics by using lasers and tunneling microscopes to break individual atomic bonds. As many people who work in scientific fields eventually discover, the research group found that it was often difficult to communicate to the uninitiated exactly what makes their work so important and interesting. For this reason, they approached Hall to commission a game that might help others understand their love of the subject.

BondBreaker, like most of Hall’s games, is free to play and is capable of running on the web, iPhone and on android. You can learn more about the game, as well as investigate the other science games available through TestTubeGames’ website.

Hall’s next project is an idea he’s been interested in for some time now. Designed to help players develop some familiarity with electromagnetism, ‘Electric Shocktopus’ focuses on an electric octopus which responds to electric and magnetic fields. In order to control the character, players will draw electromagnetic field lines on the screen and learn how to use them to get the octopus to behave the way they need it to. Hall admits that it isn’t as science-dense as BondBreaker is, but makes up for it by being incredibly addictive. Hopefully players will agree, and will come away from the experience with a little more insight than they would have garnered by playing angry birds.

Written by Aisling Williams

Source: http://blogs.scientificamerican.com/cocktail-party-physics/2014/09/09/new-bond-breaker-game-puts-you-in-the-protons-seat/