Membrane Dipole Potential: An Emerging Approach to Explore Membrane Organization and Function

Abstract

Biological membranes are complex organized molecular assemblies of lipids and proteins that provide cells and membrane-bound intracellular organelles their individual identities by morphological compartmentalization. Membrane dipole potential originates from the electrostatic potential difference within the membrane due to the nonrandom arrangement (orientation) of amphiphile and solvent (water) dipoles at the membrane interface. In this Feature Article, we will focus on the measurement of dipole potential using electrochromic fluorescent probes and highlight interesting applications. In addition, we will focus on ratiometric fluorescence microscopic imaging technique to measure dipole potential in cellular membranes, a technique that can be used to address novel problems in cell biology which are otherwise difficult to address using available approaches. We envision that membrane dipole potential could turn out to be a convenient tool in exploring the complex interplay between membrane lipids and proteins and could provide novel insights in membrane organization and function.

Cholesterol Changes Interfacial Water Alignment in Model Cell Membranes

“…Membrane dipole potential, originating from the preferential alignment of interfacial water molecules and the anisotropic orientation of lipid dipolar moieties, can reach high values of up to several hundred millivolts, leading to the formation of a strong, local electric field. It is thus of no surprise that such a dipole potential is very effective in modulating the conformation and function of membrane proteins as well as their distribution and binding affinity. , It has been shown that the membrane dipole potential is not homogeneouson the contrary, it is significantly larger in lipid domains enriched in cholesterol, correlating well with the localization of lipid raft markers within the membrane . Crucially, the spatial heterogeneity of the membrane dipole potential is interweaved with its temporal variation.…”

“…It is thus of no surprise that such a dipole potential is very effective in modulating the conformation and function of membrane proteins as well as their distribution and binding affinity. 25,26 It has been shown that the membrane dipole potential is not homogeneous�on the contrary, it is significantly larger in lipid domains enriched in cholesterol, correlating well with the localization of lipid raft markers within the membrane. 79 Crucially, the spatial heterogeneity of the membrane dipole potential is interweaved with its temporal variation.…”

“…Lipid−water interactions also affect the structure of interfacial water. Strong evidence has been found that biological water is highly polarized such that the hydrogen atoms point toward the membrane interior in the case of zwitterionic phospholipids. − The preferential arrangement of the lipid moieties and the nonrandom orientation of the associated water molecules determine the sign and magnitude of the membrane dipole potential, which was shown to strongly influence a variety of membrane-centered processes, such as drug binding, translocation of ions and macromolecules, , clustering and binding affinity of proteins as well as the function of membrane-incorporated proteins, and many more. − Furthermore, the molecular structure of biological water has been postulated to dictate the fusogenic properties of lipid membranes . In a molecular dynamics simulation study by Kasson et al, the ordering of water bound to the surface of biomembranes was found to control membrane fusion dynamics .…”

The Balance between Hydrophobicity/Aromaticity and Positively Charged Residues May Influence the Cell Penetration Ability

“…Based on these findings, it is reasonable to assume that Dabcyl might be able to reduce the membrane dipole potential and thereby enhance the cellular uptake of peptides. However, in the case of the shorter Dabcyl-conjugated oligoarginines, which enter cells mainly via lipid raft-mediated endocytosis, there is an apparent contradiction: treating cells with mBCD lowers the membrane dipole potential [43], yet the uptake of peptides is reduced. Therefore, it is an interesting question as to what is the mechanism by which Dabcyl exerts its special effect.…”

Non-destructive real-time monitoring and investigation of the self-assembly process using fluorescent probes

“…Hence, the fluorescence intensity decreases at low wavenumber and increases at high wavenumber, and the ratio of the two intensities represents a measure of the probe's response to the electric field. 95,99 For example, Haldar et al designed a voltage-sensitive probe molecule of 4-(2-(6-(dioctylamino)-2-naphthalenyl)ethenyl)-1-(3-sulfopropyl)-pyridinium inner salt (di-8-ANEPPS), which is mainly characterized by the hydrophilic receptors and two hydrocarbon chains, making the fluorescent groups parallel to the lipid molecules (Fig. 5c).…”