We further defined a HIP fold change, comparing two groups of reactions with high and low probe residence (see Methods). The results (Figure ) indicate that headgroup interactions play an important role in residence time elongation, since specific headgroup moiety interactions result in different HIP fold changes. The interactions that portray greater and more significant HIP fold changes match those exhibiting greater rate modifications in the exit kinetic measurements (Figure ), as illustrated in Figure . Heterogeneous lipid headgroup interactions appear to contribute more to residence time elongation than homogeneous interactions, further emphasizing the power of lipid mutual catalysis . Interestingly, for pairs of single-charge probes and cluster zwitterionic lipids, interactions with both zwitterionic headgroup moieties generally display substantial HIP fold changes, possibly due to the proximity of moieties on the lipid headgroup structure. Taken together, this analysis vividly displays the mechanistic interactions that underlie the observed compositionallydriven kinetic effects.