Protein-Based Optical Memories and Associative Processors

Nature has created many molecular systems which operate with efficiencies that exceed the devices made by humans.  My research group has long viewed biomolecular electronics as one of the fields of research which can provide materials and devices with comparative advantage. The Birge group at the University of California, Riverside, made the first protein-based memory in 1979, and the group has published over 50 papers in this research area during the past 38 years.  A key element in the more recent studies is the use of the protein bacteriorhodopsin to undergo a light induced photocycle coupled with the use of a second photon to switch the protein into a long-lived Q state (Birge et al., 1999pdf; Gillespie et al., 1999pdf).  The Q state is stable for 5-10 years depending upon genetic mutation, and it has a significantly different absorption spectrum and refractive index than the native protein.  This unique characteristic of bacteriorhodopsin has allowed the development of three-dimensional memories and holographic associative memories capable of high density data storage and optical associative recall and manipulation (Prokhorenko et al., 2006pdf; Greco et al., 2012pdf).

Protein-Based Retinal Implants

The development of a retinal implant is a new research area. The original design of our retinal implant was based on the use of bacteriorhodopsin to generate a photovoltaic signal (Chen et al., 1993pdf; Wagner et al. 2013).  Although this approach did induce a neural signal, the recent discovery of acid sensing channels in bipolar cells encouraged us to try a different approach.  We found that multilayer films of oriented bacteriorhodopsin showed excellent proton pumping capability and three to four times higher quantum efficiency in generating nerve impulses than the photovoltaic designs (Patent US8563026B2; Wagner et al. 2013pdf).   The retinal implant technology is currently being commercialized by LambdaVision, Inc.

Photobiology of Rhodopsin and the Cone Pigments

Study of structure and function of rhodopsin and the cone pigments has been a long term research interest.  The Birge group was the first to propose that the primary photochemical event in rhodopsin involved a barrierless or nearly barrierless process (Birge et al., 1980pdf), a proposal that was later shown to be true by femtosecond studies.   More recently we demonstrated that the counterion switch mechanism of rhodopsin is also present in the UV cone pigments (Kunsnetzow et al., 2004pdf).  A long-term interest has been the protein-chromophore interactions responsible for spectral tuning.  Our recent studies on UV (Kunsnetzow et al., 2004pdf) and deep red (Amora et al., 2008pdf) proteins has provided new insights into the mechanisms of tuning, and the role of the chromophore and the surrounding residues in the process (Sandberg et al., 2011pdf).  Much of this research has been carried out in collaboration with Dr. Barry Knox at SUNY Upstate Medical.

Directed Evolution of Bacteriorhodopsin for Applications in Bioelectronics

Although nature has optimized the native protein bacteriorhodopsin for photochemical stability and proton pumping efficiency, evolution does not optimize proteins for device environments.  Directed evolution has long been known as a powerful method of optimizing enzymes, but relatively little success has been found in using directed evolution to optimize photochromic proteins.  The problem is due in large part to the difficulty of selecting mutants that demonstrate the desired property or behavior.  Dr. Nicole Wagner in our group has developed high-throughput, automated methods of selection that permit the efficient and iterative selection of successful mutations. We have optimized the photophysical properties of bacteriorhodopsin for use in a number of device applications, including three-dimensional optical memories (Wise et al., 2002pdf), Fourier transform holographic associative processors (Hillebrecht et al., 2005pdf; Ranaghan et al., 2014pdf), photovoltaic systems (Wise et al., 2002pdf) and retinal implants (Wagner et al., 2013pdf).

Spectroscopic and Theoretical Investigations of Retinal and Carotenoid Polyenes

The primary photochemical event in rhodopsin and the cone pigments is mediated by the excitation of the polyene 11-cis retinal, and via protein-chromophore interactions.  Carotenoid polyenes also play a major roll in energy transfer in light-harvesting proteins.  Our research has provided new insights into the photophysical properties of polyenes from simple conjugated systems up to polyenes with lengths approaching the “infinite polyene” (Christensen et al., 2013pdf; Enriquez et al., 2012pdf).  We also demonstrated that the Intramolecular Charge Transfer State in peridinin was an evolved state rather than a stationary state of peridinin (Wagner et al., 2013pdf). Dr. Jordan Greco in our group has recently investigated the forbidden 11Ag– (S0) to 21Ag– (S1) and 11Ag– (S0) to 11Bu– (S3) transitions of peridinin analogues (Greco et al., 2016pdf; Greco et al., 2018pdf)