Current Methods for Detecting Cell Membrane Transient Interactions

Abstract

Short-lived cell membrane complexes play a key role in regulating cell signaling and communication. Many of these complexes are formed based on low-affinity and transient interactions among various lipids and proteins. New techniques have emerged to study these previously overlooked membrane transient interactions. Exciting functions of these transient interactions have been discovered in cellular events such as immune signaling, host–pathogen interactions, and diseases such as cancer. In this review, we have summarized current experimental methods that allow us to detect and analyze short-lived cell membrane protein–protein, lipid–protein, and lipid–lipid interactions. These methods can provide useful information about the strengths, kinetics, and/or spatial patterns of membrane transient interactions. However, each method also has its own limitations. We hope this review can be used as a guideline to help the audience to choose proper approaches for studying membrane transient interactions in different membrane trafficking and cell signaling events.

Interactions of Amyloid-β with Membrane Proteins

“…When describing the interactions of amyloid with proteins of cell membranes, it is impossible not to mention the methods of studying their kinetics and spatial patterns. Interaction research methods can be divided into computational and experimental [ 70 ].…”

“…Commonly used experimental methods to study membrane interactions are nuclear magnetic resonance spectroscopy, mass spectrometry, fluorescence correlation spectroscopy and cross-correlation spectroscopy, super-resolution microscopy, Förster resonance energy transfer, membrane two-hybrid assays and photoactivatable or DNA-based lipid probes [ 70 ]. Nuclear magnetic resonance spectroscopy allows the analysis of the structure, dynamics, binding site and affinity of the protein–cell membrane complexes [ 72 ].…”

“…The disadvantage of this method is also the time-consuming analysis of the results—the larger the protein, the longer the analysis, which can take up to several days. Moreover, the need to use detergents in this method may also lead to misinterpretation of the obtained results, and interaction studies cannot be performed on living cells, contrary to NMR [ 70 ].…”

“…The method of fluorescence correlation spectroscopy, which allows the real-time study of cell membrane–ligand interactions, uses fluorescently labeled compounds that interact with the membrane [ 74 ]. The greatest disadvantage of this method is that it requires at least eight times the difference in molecular weight between the bound and unbound states [ 70 ]. A solution to this difficulty may be the use of fluorescence cross-correlation spectroscopy, which measures the correlation of two fluorescently labeled compounds [ 74 ].…”

“…A solution to this difficulty may be the use of fluorescence cross-correlation spectroscopy, which measures the correlation of two fluorescently labeled compounds [ 74 ]. However, both of these fluorescence spectroscopy methods are not suitable for monitoring slowly moving membrane proteins [ 70 ].…”