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!
Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology