טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentArbel Artzy-Schnirman
SubjectThe Bio-Electronic Synapse: Electrical Control over
Biological Processes by Molecular Recognition
of an Electronic Device
DepartmentDepartment of Biology
Supervisors Full Professor Sivan Uri
Full Professor Reiter Yoram
Full Thesis textFull thesis text - English Version


Abstract


Learning a lesson from biology where interfaces and decisions are realized through mutual recognition of two molecules we propose and demonstrate a generic functional interface between electronics and biology. In our bio-electronic synapse one of the recognizing molecules is replaced by a self-assembled Hydroquinone (HQ) monolayer on gold while for the other molecule we choose an antibody selected in-vitro from a phage display library to discriminate between the two oxidation states of the monolayer. Application of .6V pulse to the gold sets the monolayer in its "on", oxidized state Benzoquinone (BQ), where the antibody binds the device. A subsequent application of -0.6V pulse to the same device turns it back to its "off", reduced state (HQ), where the antibody detaches from the device.

Using electrochemical Surface Plasmon Resonance (SPR) combined with mutagenesis of the antibody, the binding of the antibody to the monolayer is traced to electrically controlled hydrophobic interactions between a particular phenylalanine residue on CDR3 of the antibody and the hydrophobic BQ ring. In the reduced, non-binding HQ state (C6O2H6), the two hydrogen atoms form two strong hydrogen bonds with surrounding water molecules and shield the ring from binding to the phenylalanine residue. The loss of two hydrogen atoms upon oxidation to BQ (C6O2H4) leads to the release of two water molecules thus facilitating hydrophobic interaction between the antibody and the BQ ring. Measurements of the change in water index of refraction next to the monolayer show reduction in index of refraction which is consistent with the release of two water molecules per ring in the oxidation process.

The demonstrated bio-electronic synapse is harnessed in the second part of the work to gain electrical control over a major biological process- activation of T-cell response to that end, the isolated antibody is fused with a T-cell receptor to produce T-cells that discriminate between the two electronic states of the bio-electronic synapse. Upon application of a .6V pulse to the gold, the HQ oxidizes to BQ and the T-cells activate upon recognizing the device. This success constitutes the first demonstration of electrical control over a biological process via control over the underlying molecular recognition.