We are using our expertise in sensitive force measurement techniques to study the interaction between single molecules involved in signal transmission in the human brain.  This is collaborative research done with biologists. In particular we have focused on the interaction of proteins that lead to the release of neurotransmitters, which is still poorly understood. Single molecule techniques are ideal as we demonstrated that only one set, is sufficient to anchor the neurotransmitter containing vesicles to the plasma membrane of neurons. In addition, we have used the technique to prove the Jarzynski equality of non equilibrium thermodynamics. This theorem provides a method to obtain equilibrium energies from nonequilibrium measurements as encountered in all single molecule studies. It is applicable only to microscopic systems and thus is ideal for single molecule systems. Prior to our work there was one demonstration using optical tweezers and a single RNA attached to beads with long linkers.

 

Our AFM based single molecule demonstration used:

(i) point like rigid attachment of the molecules without linkers,

(ii) was applied to intermolecular bonds and used

(iii) the temperature dependence of the binding energy to confirm the approach to the adiabatic limit.  We have also used our single molecule detection sensitivity to design a detector for neurotoxins. This was published in the Proceedings of the National Academy of Sciences.  More recently, we are using similar techniques as above to understand the kinetics of the self assembly of viruses.

Biophysics