Table 1.

Solution-based techniques to detect PLI

Methods	Advantages	Disadvantages
Liposome sedimentation assay	Applicable for proteomics analyses (in vitro and in vivo); available as both label-free and label-based methods.	Difficult to quantify the equilibrium constants.
Photoactivated cross-linking assay	Applicable for proteomics analyses (in vitro and in vivo).	Low sensitivity (provides low yield of the cross-linked lipid-binding proteins).
Isothermal titration calorimetry (ITC)	Provides thermodynamic parameters; is a label-free method.	Low sensitivity (requires higher protein concentrations).
Electron spin resonance (ESR) spectroscopy	Provides stoichiometry, selectivity, and geometric information of PLI; can be applied on opaque samples.	Requires post-hoc molecular modification that limits the applicability of the approach in biological membranes.
Fluorescence-based assays	Higher sensitivity.	Problems with light scattering and auto-fluorescence.