The dynamic HIP analysis shows the percentage of reactions in which a specific headgroup interaction is present at each time-step during the probe residence. We calculated these values for probes interacting with modulatorrich and modulator-poor clusters, and plotted the difference (HIP shift) between these two groups (Figure , Supp. Figure ). The results indicate that elevated levels of modulator lipids in clusters indeed promote the majority of probe-modulator headgroup interactions, which is most prominent in chemistries that match substantial exit rate modifications. The analysis demonstrates how probes become engulfed in the cluster during their residence (Figure , 4D), interacting selectively with neighboring lipids. The gradual changes in HIP shift throughout the residence, especially for kinetically-affected chemistries (e.g. SDS-DDA), suggest that higher modulator concentration in clusters make these interactions more intensive within the pre-micellar cluster than in the transition states (at the beginning and end of the probe residence). Thus it can be expected that the energy state of the probe within the cluster is more affected by compositional variation than that of the transition state.