Robert Raphael investigates how the coupling between mechanical, electrical and transport properties of biomembranes regulates cellular processes. Through basic research into biological membranes and the intricate workings of the inner ear, his group is producing new insights into the causes of hearing loss and deafness, and is inspiring new ideas into the design of biosensors and microscale biomedical devices.
Raphael's research combines advanced optical microscopy, electrophysiology and micromechanical techniques to study the cellular and molecular basis of auditory function, including the electroactive motor protein prestin and inner ear ion homeostasis. He is involved in an ongoing project aimed at understanding the mechanism by which prestin operates in the membrane, and how aspirin-like molecules affect membrane mechanics. His group has developed the first biophysically-based computational model of potassium transport in the inner ear.
Raphael has received several honors for research and education, including an NSF CAREER Award (2005), two Hamill Innovation Awards (2006, 2007) from the Institute of Biosciences and Bioengineering (IBB), the Faculty Teaching/Mentoring Award from the Rice Student Association (2007), the Charles W. Duncan Jr. Achievement Award for Outstanding Faculty (2010), and a Collaborative Research Award from the John S. Dunn Foundation (2018).
Investigations in Raphael's Membrane and Auditory Bioengineering Group are currently focused on three major inter-related areas:
Cochlear outer hair cells and soft materials cochlear outer hair cells are biological microelectromechanical systems (MEMs) that possess a unique membrane motor protein (prestin) that generates force in response to changes in membrane potential. Damage to these cells causes many forms of hearing loss. Raphael has constructed a thermodynamic liquid crystal model of this process based on electrically-induced nanoscale curvature changes in the membrane (flexoelectricity). Raphael is also interested in preventing the degeneration of outer hair cells and cell-cell interactions in the cochlea.
Aspirin-Like Molecules and Membrane Mechanics
Using the technique of micropipette aspiration, Raphael discovered that salicylate, the metabolite of aspirin, softens lipid membranes. This effect may explain side effects of aspirin ingestion not attribution to the inhibition of cyclooxygenase, such as ototoxicity. The work is being extended to other aspirin-like molecules and computational and molecular models are being developed to understand the temporal features of these effects. The project illustrates how surfactant and interfacial science are germane to bioengineering problems and how mechanochemical coupling can influence biological processes. In addition, aspirin-induced softening of cell membranes can be used as a modulator of membrane function.
Biophysical Factors Mediating Gene Delivery
Viral-mediated gene delivery has many disadvantages and there is a need to develop safe and efficient nonviral methods for molecular transfer. The composition and mechanical properties of membranes determine the ability of electric fields to facilitate molecular transfer across the membrane (electroporation) and for membranes to fuse. Agents that soften the membrane such as aspirin can decrease the electroporation threshold, and research is aimed at correlating this with cell mechanical properties and developing biophysical models of the process. Another method for the delivery of agents to cells is by encapsulating them in liposomes. Raphael has designed a liposome capable of interacting with the cochlear outer hair cell, illustrating how molecular engineering of the membrane holds the promise to improve liposomal mediated delivery in tissue engineering applications.