Table 1.

Currently available methods for studying cell membrane transient interactions.

Method	Resolution		Membranes applied		Interactions studied	Interaction information provided
	Temporal	Spatial	Cell	Synthetic
NMR	ms	Atomic	No	Yes	Lipid–protein Protein–protein	Structure and conformation Kinetic and equilibrium constant
HDX-MS	ms	μm	No	Yes	Lipid–protein Protein–protein	Protein conformation Stoichiometry
SIMS	min	100 nm	Yes	Yes	Lipid–lipid Lipid–protein	Membrane distribution
FCS and FCCS	μs	200 nm	Yes	Yes	Lipid–lipid Lipid–protein Protein–protein	Membrane concentration Membrane distribution Kinetic and equilibrium constant
STED-FCS	μs	20 nm	Yes	Yes	Lipid–lipid Lipid–protein Protein–protein	Membrane concentration Membrane distribution Kinetic and equilibrium constant
TIRF	μs	20 nm	Yes	Yes	Lipid–lipid Lipid–protein Protein–protein	Membrane distribution Kinetic and equilibrium constant
FRET	μs	10 nm	Yes	Yes	Lipid–lipid Lipid–protein Protein–protein	Membrane distribution Kinetic and equilibrium constant
FLIM-FRET	s	10 nm	Yes	Yes	Protein–protein	Membrane distribution Kinetic and equilibrium constant
MTH	s	200 nm	Yes	Yes	Protein–protein	High-throughput screening
PAL	ms	μm	Yes	Yes	Lipid–protein	Proteome-wide profiling Protein–lipid complex structure
DNA probe	μs	10 nm	Yes	Yes	Lipid–lipid Protein–protein	Membrane distribution Kinetic and equilibrium constant

MTH, membrane two-hybrid assay; PAL, photoactivable lipid probe.