UCSB's Reich Group uses lasers to spatially and temporally control the release of a tagged protein inside a cell
Optogenetics, which uses light to control cellular events, is poised to become an important technology in molecular biology and beyond. The Reich Group in UC Santa Barbara's Department of Chemistry and Biochemistry has made a major contribution to this emergent field by developing a light-activated nanocarrier that transports proteins into cells and releases them on command. The findings appear in the journal Molecular Pharmaceutics.
Using inorganic gold nanoshells and a near-infrared laser, UCSB biochemistry professor Norbert Reich and graduate student Demosthenes Morales demonstrate for the first time a method that affords both spatial and temporal control over protein delivery in cells.
"You can point the laser at cells where and when you want a particular protein to be turned on," Reich said. "And that means you can ask biological questions that you could never ask before because you're able to say I want this one cell to do this."
The researchers exploited the receptors on prostate cancer cells, which rely on the recognition of a C-end rule internalizing peptide that has been fused to the end of a green fluorescent protein. This peptide is very specific for the receptor and once the two meet, it actually takes in the protein-loaded nanoparticles and shepherds them into the cell via endocytosis, a process that brings large molecules into cells.
The team used a modular nickel linking layer on the surface of the nanoparticles that is able to support different kinds of proteins fused with a polyhistidine tag commonly found on proteins expressed in labs. "We want this to be applicable to any type of protein that has a polyhistidine tail," lead author Morales said, "so if you synthesize or grow proteins in a lab, you can easily load the protein onto our nanoparticles."
While the Reich Group's hollow gold nanoshells are effective carriers, transporting large biomolecules such as proteins into cells is only half the battle. In order for the protein to be effective once inside the cell, it must be released from the vesicle (endosome) holding it. The UCSB design enables that to happen.
When we excite these hollow gold nanoshells with light, the surface of the nanoparticle becomes somewhat hot," Morales said. "The light not only releases the cargo that's on the surface but also causes the formation of vapor bubbles, which expand and eventually pop the vesicle, allowing for endosome escape."
The Reich Group's construct is designed around the advantage of protein delivery's specificity. "The best thing about our platform is that it has a wide range of applicability," Morales noted. "Not only do we have the ability to target with a laser where and when we want to release our therapeutic, but we also leverage the fact that the protein itself is very specific. We have specificity in terms of time and we have specificity toward the target. This is why proteins are very fascinating as a potent therapeutic."
According to Reich, this technology has important implications for basic research. "Biologists are going to make use of this kind of technology but they aren't going to develop it," Reich said. "There are a few people on campus who could use this technology so we have a unique opportunity at UCSB to be the lead in interfacing between the developers and the users."
Julie Cohen | EurekAlert!
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences