Skip to the ****’s if you already know what micelles are and want to get to the cool part.
Micelles are what allow soap to lift off grease - those white orbs are attracted to water (hydrophic), but their tails are repelled by it (hydrophobic). This happens when lipids encounter fluid - the polar heads face towards the aqueous (polar) surrounding, and the hydrophobic tails naturally avoid the water. What kind of ‘structure’ the clustering of lipids make in reaction to water depends on the lipid’s concentration. The result of their clustering together is the formation of vesicles in the center - that bubble of space in the center, which you might remember for learning cells in biology class - they not only affect the structure’s bouyancy and movement, but also their metabolism because the lipid bilayer that surrounds them enacts a kind of intelligent osmosis; absorbing what’s needing and holding in or rejecting ions/proteins/molecules as required.
As a result, vesicles are used both naturally and in medicine to transport things like proteins or drugs to various cells in the body.
The above is a molecular dynamics simulation of a graphene sheets hosted within a vesicle. The research, conducted at the University of Illinois and published at the end of 2009, concluded following simulations that graphene can be integrated into micelles to form a 'hybrid graphene-membrane superstructure’, allowing electrical and digital structures to move through biological systems within a waterproof structure accepted as natural by the organism.
Other crazy research with micelles was conducted in Germany, suggesting that micelles could contain protocells - non-living organisms capable of metabolizing and often producing materials (There’s some really interesting architectural research on this figureheaded by Rachel Armstrong.) The study supposes that
“the information stored in the PNA influences the functioning of the metabolism, turning the template intoan actual genome. The protocell grows with the incorporated nutrients. With the reach of a critical size, the container becomes unstable and divides into two daughter cells. Supposed that nutrients are provided in the right stoichiometric ratio, the two daughter cells will be replicates of the original organism[…allowing it to] build vitro as a minimal molecular machine, able to undergo self replication and ﬁnally, evolution.”
In short, we’re reaching a level of blending between digitizable materials (ie graphene) and biological materials that, may I say, is fairly cyborgy. But it’s also part of a fairly nearby future in which nanomedicine becomes a more everyday part of care, cities and their structures intelligently process energy without waste, everybody owns a Roomba…
So what I’m saying is, how about we take some micelles, fill em up with graphene and protocells, instate programs in the graphene which trigger an intelligence to the protocells, who then absorb CO2 and transform it into a limestone like structure, underwater, get ourselves an underwater city in like two days or so?
–Subject to continuous editing as I figure out what the hell is going on in the world. (Rachel Armstrong has been contacted).–
Sorry I haven’t been updating more often! I have been fairly busy learning a ton of new things to share with all of you.
Well here is a beautiful picture of what a micelle would look like. A Micelle is one of the very first ideas that people have had for a drug delivery system. The thing that makes it so perfect is the combination of its self forming properties due to hydrophobic effects and its ability to get through the lipid bilayer. By doing this, we can delivery drugs with poor solubility.
That’s a short blurb about micelles, but this is just the beginning! I have so much more to share with you all both about drug delivery and just my experiences.
80% of the protein in milk is casein, and it doesn’t simply exist as monomers of globular protein in solution. The 4 types of casein form spherical aggregates averaging ~150nm in diameter containing calcium-phosphate nanoclusters called casein micelles (which are distinct from lipid micelles). Though a lot of research had been done on the structure of the casein micelles, it remained unresolved. Synchrotron radiation at an energy range around the absorbance edges of the calcium in a resonant soft x-ray scattering (RSoXS) experiment was used to help clarify interpretation of previous scattering results, because the features observed would be predominantly from the most common calcium-containing material in milk, the casein micelles. It showed that a scattering peak previously observed by small angle neutron scattering (SANS) could be modeled by inter-particle scattering between the calcium phosphate nanoclusters, and that a feature previously observed by small angle x-ray scattering (SAXS) that was previously attrbuted to Ca-PO4 nanocluster shape was not present, meaning that it may have been due to inhomogeneity in protein density on the 1-3nm scale.
In the game Angry Birds, destroying the evil pigs’ fortress isn’t always straightforward. Often, rather than attacking the tough exterior, it’s best to launch a bird through tiny gaps in the walls and strike at the heart of the problem. But then, which bird to choose? Cancer biologists are experimenting with ways to shoot drug carriers through small holes in the walls of tumours. Here are depicted tiny spherical containers called micelles injected into the blood vessels supplying the tumour of a mouse. Differently-sized micelles are stained green (each measuring 3/100,000 cm across) and red (7/100,000 cm across) giving the vessel a bright yellow appearance. Only the green micelles are small enough to fly through the holes in the tumour wall and spread out fully into the cancer. Tiny micelles might one day be used to deliver a chemotherapy payload straight into the heart of human cancers.
Chemists at the University of Oxford, UK, have developed a way to look at the cell’s membrane lipids without using detergents — charged molecules which can interfere with exactly those structures they are being used to visualise.
In the illustration above: Lipid heads at the top and bottom of the bilayers (purple dots); the protein belt used to protect lipid tails from coming into contact with water (cyan); and the membrane protein encapsulated in the centre (red). The disc encased in a charged water droplet (right) undergoes evaporation to form the naked disc (left) which can then be studied in a mass spectrometer.
Membrane proteins are key to many biological processes and comprise half of all current drug targets. They are notoriously difficult to study in their natural environment (see my previous post on reverse micelles), but this new technique has allowed just that — combining the use of sophisticated nanodiscs with mass spectrometry.
some detergents can promote unfolding, and they do not mimic the lateral forces and curvature of the cellular membrane that can be important for maintaining protein structure… nanodiscs and bicelles that employ small, discoidal arrangements of phospholipid bilayers have demonstrated great potential for X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy and electron microscopy.
The study confirmed that “oligomeric complexes or proteins requiring defined lipid environments are stabilized to a greater extent in the absence of detergent”. The team set themselves a challenge in selecting proteins known to be tricky analytes:
To test the preservation of oligomeric state, we analyzed E. coli diacylglycerol kinase (DgkA), a trimeric cytoplasmic membrane protein9 whose activity and oligomeric state varies based on its preparation10 and the presence of lipids11 . The third protein we studied, sensory rhodopsin II (pSRII) from Natronomonas pharaonis, is a seven-transmembrane (7-TM) receptor of negative phototaxis12,13 ; this protein represents a ubiquitous yet notoriously unstable class of membrane protein…
DgkA, pSRII and LacYGFP were released from micelles possessing average charge states of 7+, 9+ and 18+, respectively, indicative of compact structures. Unfolded proteins, with larger surface areas and/or more exposed basic residues, result in a wider charge-state distribution centered around higher charge. For DgkA, we observed the monomeric protein to be dominant, with a smaller population corresponding to dimers. However, the expected stoichiometry of DgkA is trimeric, indicating that detergent micelles are inadequate for preserving this complex in the gas phasep>s.
Using a high-tech nano flow system, molecules are transmitted into the instrument in charged water droplets, which then undergo evaporation releasing molecules into the gas phase of the mass spectrometer.
Hydrophobic membrane proteins pose a problem to this method, as by their very nature they won’t dissolve in water, leading to the common use of detergents to force them to do so, however this can damage the protein’s structure making it an unreliable model of the in vivo reality.
First author John Hopper explains on his faculty website that nanodiscs are tiny disc-like structures made of lipids…
…the same material that membrane proteins occupy in the body. It’s essentially as if you took a round cookie cutter to remove a section of the natural bilayer, so the conditions are just like they would be in the body. The discs are stabilised by wrapping a belt of proteins around them to keep the exposed lipid tails from the water.
They consist of a segment of bilayer encapsulated by an amphipathic protein coat, rather than a lipid or detergent layer. Nanodiscs are more stable than bicelles and micelles at low concentrations, and have a well-defined size (10-20 nm, depending on the type of protein coat).
As an alternative to using bicelles, we next assembled membrane scaffold protein 1D1 (MSP1D1) nanodiscs (following established protocols16 ), to solubilize the target protein. MSP1D1 nanodiscs also provide a lipid bilayer environment, in this case DMPC. The hydrophobic perimeter of a nanodisc is stabilized by two copies of a long α-helical membrane scaffold protein (MSP). Measurements of dynamic light scattering revealed homogeneous size distributions (Supplementary Fig. 9), and transmission electron microscopy (TEM) showed uniformly sized disc structures, some in face-to-face stacked arrangements, of the correct geometry. LacY-GFP allowed us to monitor its incorporation into membrane scaffold protein 1E3D1 (MSP1E3D1) nanodiscs through size exclusion chromatography and affinity purification (SupplementaryFig. 1). We observed a series of charge states for LacY-GFP (3+ to 5+, Supplementary Fig. 11) from nanodiscs (compare to 14+ to 21+ from DDM micelles, Supplementary Fig. 5), implying that in nanodiscs LacY is folded and undergoes extensive lipid binding… Mass spectra (CE of 400 V) clearly showed the presence of well-defined trimers as well as monomers and dimers of DgkA.
…The low charge states observed for proteins ejected from nanodiscs or bicelles, compared with those from micelles, minimize the potential for coulomb-induced unfolding in the gas phase. Both nanodiscs and bicelles maintained the native trimeric stoichiometry of DgkA, though a larger population of trimeric assemblies was preserved after dissociation from bicelles compared with nanodiscs (Figs. 1c and 2c). Larger bicelles, presumably with greater lateral forces that effectively ‘compress’ the protein subunits along the plane of lipid bilayer, could maintain dimeric forms of pSRII.
Hopper explains further on the UoOx site,
Aside from the nanodiscs, we actually got great results from bicelles, which are made in a similar way. The main difference is that instead of putting a belt of proteins around the edge, we plug the gap with short-chain lipids instead. This actually gives us much more control over the size and structure of the disc.
The paper itself however is more critical of bicelles, highlighting that “both nanodiscs and bicelles have the ability to preserve protein-lipid interactions, although the range of lipids that can be explored is limited for bicelles.”.
Figures below show some of the interesting conformations the molecules involved take on during these experiments (amphipols = amphipathic polymers)
A DIALOGUE WITH SARAH, AGED 3: IN WHICH IT IS SHOWN THAT IF YOUR DAD IS A CHEMISTRY PROFESSOR, ASKING “WHY” CAN BE DANGEROUS By Stephen McNeil
SARAH:Daddy, were you in the shower?
DAD:Yes, I was in the shower.
DAD:I was dirty. The shower gets me clean.
DAD:Why does the shower get me clean?
DAD:Because the water washes the dirt away when I use soap.
DAD:Why do I use soap?
DAD:Because the soap grabs the dirt and lets the water wash it off.
DAD:Why does the soap grab the dirt?
DAD:Because soap is a surfactant.
DAD:Why is soap a surfactant?
DAD:That is an EXCELLENT question. Soap is a surfactant because it forms water-soluble micelles that trap the otherwise insoluble dirt and oil particles.
DAD:Why does soap form micelles?
DAD:Soap molecules are long chains with a polar, hydrophilic head and a non-polar, hydrophobic tail. Can you say ‘hydrophilic’?
DAD:And can you say ‘hydrophobic’?
DAD:Excellent! The word ‘hydrophobic’ means that it avoids water.
DAD:Why does it mean that?
DAD:It’s Greek! ‘Hydro’ means water and ‘phobic’ means ‘fear of’. ‘Phobos’ is fear. So ‘hydrophobic’ means ‘afraid of water’.
SARAH:Like a monster?
DAD:You mean, like being afraid of a monster?
DAD:A scary monster, sure. If you were afraid of a monster, a Greek person would say you were gorgophobic.
SARAH:(rolls her eyes) I thought we were talking about soap.
DAD:We are talking about soap.
DAD:Why do the molecules have a hydrophilic head and a hydrophobic tail?
DAD:Because the C-O bonds in the head are highly polar, and the C-H bonds in the tail are effectively non-polar.
DAD:Because while carbon and hydrogen have almost the same electronegativity, oxygen is far more electronegative, thereby polarizing the C-O bonds.
DAD:Why is oxygen more electronegative than carbon and hydrogen?
DAD:That’s complicated. There are different answers to that question, depending on whether you’re talking about the Pauling or Mulliken electronegativity scales. The Pauling scale is based on homo- versus heteronuclear bond strength differences, while the Mulliken scale is based on the atomic properties of electron affinity and ionization energy. But it really all comes down to effective nuclear charge. The valence electrons in an oxygen atom have a lower energy than those of a carbon atom, and electrons shared between them are held more tightly to the oxygen, because electrons in an oxygen atom experience a greater nuclear charge and therefore a stronger attraction to the atomic nucleus! Cool, huh?