Triskelia are the tripod shaped subunits of Clathrin. The Clathrin protein self-assembles into nanoscale spheres that lase “Our clathrin scaffolding applications are also dual use, with commercial applications in VLSI lithography, biomolecular electronics and in self-assembling novel photonic nanostructures for alternative energy generation
* Clathrin, a protein found in every cell of the human body, could become a self-assembler of future information processing systems that are smaller, faster and cheaper than today’s computer circuitry
* Boston-based ExQor Technologies said it has demonstrated that Clathrin can be formed into nano-sized biolasers suitable for transmitting information. It expects the technology will initially be used in medical applications.
ExQor’s patented bio-nanolasers (as small as 25 nm) can be functionalized with ligands, enzymes, peptides, etc., and used to kill cancer cells, destroy blood clots in hard to reach locations, and act as diagnostic sensors.
One very exciting prospect is using ExQor’s nano-lasers for repairing and growing neurons in the human nervous system.
Another powerful application for ExQor’s nanolasers is disposable, safe, ultrasensitive, ultrafast biochips for DNA and RNA detection.
The protein clathrin exists in the cells of most living things as a gate-keeper and signaling system. It sorts and transports chemicals by folding around them as they enter a cell. Individual clathrin subunits, called triskelion, are shaped like a tripod.
In solution, ExQor’s synthetic version self-assembles a number of triskelia into 20- to 100-nanometer diameter cages containing “cargo.” By functionalizing the triskelia with antibodies or other agents that identify pathogenic conditions like cancer or tissue damage, clathrin cages can carry drugs to specific cells, then pass inside to deliver them.
Since clathrin is a natural gatekeeper in the body, it can readily access most human cells, even safely entering the brain, which normally prevents large molecule drugs from entering.
While researching clathrin for medical applications, ExQor discovered that the material exhibits quantum properties useful for biocomputing applications, including nanoscale lasing.
“When we were first developing the clathrin asymmetric resonant cavity, or ARC, we could not find any other research into lasing at scales as small as ours–below 100 nanometers,” said Vitaliano. “Most scientists at the time believed that structures at that scale could not support lasing, but now we know it can using cavity quantum electrodynamics.”
The nano-lasing property will initially be used in energy applications to produce self-generated light to prevent the buildup of industrial biofilm by killing the culprit organisms. Another potential application is nanoscale photonics. The researchers also claim that other quantum computing phenomena, for which ExQor has been granted U.S. patents, will enable novel spin-based, self-assembling nano-electronic devices that could exceed the performance of planned nanoscale devices using traditional inorganic materials.
“Our aspiration is to enable bio-based quantum computing at the nanoscale [level] by using the same completely reversible processes that keep heat to a minimum in living things,” said Vitaliano.
The researchers also are investigating intermolecular multiple quantum coherence and intermolecular zero quantum coherence, methods currently used to enhance the contrast of conventional magnetic resonance imaging, and as signposts for initiating and controlling quantum effects in the body.
ExQor Patents and Research
US Patent 7216038 – The invention in various embodiments is directed to quantum information processing elements and quantum information processing platforms employing such elements. In one aspect, the quantum information processing elements are formed with self-assembling protein molecules.
An isolated quantum information processing element comprising a cage, up to 100 nanometers in diameter, defining a cavity formed from a plurality of self-assembling purified Clathrin protein molecules, and one or more cargo elements located within the cavity, wherein at least one of the cargo elements comprises a qubit programmable into one or more logical states.
The US Patent 7393924 – invention in suitable embodiments is directed to isolated bio-nanoparticle elements and isolated bio-nanoparticle platforms employing such isolated bio-nanoparticle elements. In one aspect, the isolated bio-nanoparticle elements are formed with purified Clathrin and or with purified coatomer I/II self-assembling protein molecules.
Background: Magnetic Resonance Imaging is a noninvasive visualization technique with high spatial resolution, but low sensitivity for visualization of molecular targets. In order to improve MRI sensitivity for molecular brain imaging, our goal was to develop clathrin-based nanoprobes with high molecular relaxivity that incorporate high payloads of Gadolinium (Gd) contrast agents, which can be delivered non-invasively and target specific receptors in the rat brain. Methods: Gadolinium-DTPA-ITC was conjugated to clathrin cages through reactive lysine residues. We determined the chelate to protein molar ratio by using a standard spectrophotometric method based on the reaction between a DTPA-ITC ligand protein conjugate and an yttrium (III) complex of Arsenazo III. Relaxivity for each sample was calculated using T1 data and gadolinium concentration as determined by NMR analysis. Maleimide-PEG-Dopamine-3 Antibody (D3Ab) and Maleimide-PEG-rhodamine conjugates were prepared, clathrin-nanoparticles were PEGylated and delivered intranasally. Animals were sacrificed 3 hours after intranasal administration of D3Ab-labeled fluorescent Clathrin nanoparticles. Results: Electron Microscopy has shown a large proportion of Gd-DTPA-clathrin cages that form hexagonal barrels 52 nm in size. The mean Ligand/Protein molar ratio was 27±2.4. At 0.47T, Gd-DTPA-ITC-Clathrin-Cages displayed relaxivity of 283,176mM-1s-1 per particle, and 97mM-1s-1 per Gd ion. Three hours after intranasal administration D3Ab-labeled Clathrin nanoparticles were found only in D3 related brain regions in rats. Fluorescent and light microscopic examination of the D3 brain regions confirmed specific targeting of the D3 receptors with D3Ab-nanoprobes. Confocal laser microscopy confirmed integrity of the nanoparticles in the rat brain. Clathrin and D3Ab florescence co-localized in the D3 brain regions. Conclusions: New Clathrin nanoparticles displayed an unusually high molecular relaxivity, were successfully delivered non-invasively nasally into the rat brain, were able to target specific receptors, and remained stable in the rat brain. They showed over 50,000-fold greater molecular relaxivity than any currently approved Gd-MRI contrast agent. These preliminary results should encourage further investigations into the use of clathrin cages as a new nanoplatform for MR contrast enhanced molecular brain imaging.
Dr. Sarah Heilshorn of the Stanford Institute of Materials and Energy Science, a joint SLAC and Stanford venture, is interested in investigating the capabilities of this nifty protein (clathrin) in collaboration with SIMES colleagues Nick Melosh, Andy Spakowitz and Seb Doniach. The scientists are curious how clathrin might be used to form nanostructured inorganic materials for applications in batteries and solar cells. This protein can essentially be used as a skeletal template for the growth of inorganic materials into precise structures. Once scientists assemble the clathrin protein into the proper structures, they can attach other atoms and molecules, much like adding windows and walls to the frame of a house.
Clathrin Structure Reveals Motifs for Self-Assembly
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