Robert Raphael approaches scientific problems in a multidisciplinary spirit, employing both theory and experiment to understand biological processes at the fundamental level and apply this knowledge for the benefit of human health. He is currently focused on three major inter-related questions:

1) Electromechanical Transduction in 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. Dr. Raphael has constructed a thermodynamic liquid crystal model of this process based on electrically-induced nanoscale curvature changes in the membrane (flexoelectricity). He is involved in a collaborative project with Baylor College of Medicine aimed at elucidating the mechanism by which Prestin operates in the membrane. This work involves modeling membrane/cytoskeletal association, tether formation with optical tweezers and developing new techniques for evaluating nanoscale membrane mechanics. The project has tremendous engineering potential because Prestin can be used in the design of synthetic MEMs made of biocompatible materials. Dr. Raphael is also interested in the prevention of degeneration of outer hair cells and cell-cell interactions in the cochlea.

2) Aspirin-Like Molecules and Membrane Mechanics

Using the technique of micropipette aspiration, Dr. 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.

3) 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. Dr. 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.