In this project, we are studying the thermodynamic basis of membrane protein association in lipid membranes.  In many cases of soluble protein association, binding is driven by the hydrophobic effect, an entropic drive that arises from burying greasy residues away from water.  However, this cannot apply to the association of membrane proteins as membranes are comprised of oil.  Why then do greasy membrane proteins choose to interact with other greasy protein surfaces over the similarly greasy lipid solvent?  Recently, we developed a method to measure the free energy of association of high-affinity membrane protein complexes by passive dilution using single-molecule microscopy approaches (Chadda & Robertson, MIE 2016).  We have applied this to study the dimerization of the large CLC-ec1 antiporter, showing that it is one of the most stable membrane protein complexes studied so far (Chadda et al., eLife 2016; Chadda et al., JGP 2018).  We are now using this as a model system for dissecting the thermodynamic driving forces underlying this strong affinity, and identifying how changes in protein or lipids affects the reaction.  Furthermore, we are now studying other membrane protein complexes, to expand on the model systems available for thermodynamic investigation. 

In the past, this research has been supported by NIH K99/R00 GM101016 and a Carver Trust Young Investigator Award.  It is currently supported by NIH R01 GM120260.