Abstract
When two oppositely charged macroions are brought into contact, a large fraction of the mobile counterions that previously surrounded each isolated macromolecule is released into the bulk solution, thereby increasing the counterions' translational entropy. The entropy gain associated with this counterion release mechanism is the driving force for various macroion binding processes, such as protein–membrane, protein–DNA, and DNA–membrane complexation. In this review we focus on the role of counterion release in the interaction between charged macromolecules and oppositely charged lipid membranes. The electrostatic interaction is generally coupled to other degrees of freedom of the membrane, or of the adsorbed macroion. Thus, for example, when a basic protein adsorbs onto a binary fluid membrane comprising anionic and neutral lipids then, in addition to the release of the mobile counterions to the bulk solution, the protein polarizes the membrane composition by attracting the charged lipids to its immediate vicinity. This process, which enhances the electrostatic attraction, is partly hampered by the concomitant loss of two-dimensional (2D) lipid mixing entropy, so that the resulting lipid distribution reflects the balance between these opposing tendencies. In membranes containing both monovalent and multivalent lipids, as is often the case with biological membranes, the peripheral protein preferentially interacts with (and thus immobilizes) the multivalent lipids, because a smaller number of these lipids are needed to neutralize its charge. The monovalent “counterlipids” are thus free to translate in the remaining area of the membrane. This entropy-driven counterlipid release mechanism in 2D is analogous to the extensively studied phenomenon of DNA condensation by polyvalent cations in 3D. Being self-assembled fluid aggregates, lipid bilayers can respond to interactions with peripheral or integral (whether charged or neutral) macromolecules in various ways. Of particular interest in this review is the interplay between electrostatic interactions, the lipid composition degrees of freedom mentioned above, and the membrane curvature elasticity, as will be discussed in some detail in the context of the thermodynamic stability and phase behavior of lipid–DNA complexes (also known as “lipoplexes”). This article is primarily theoretical, but the systems and phenomena considered are directly related to and motivated by specific experiments. The theoretical modeling is generally based on mean-field level approaches, specifically the Poisson–Boltzmann theory for electrostatic interactions, sometimes in conjunction with coarse grained computer simulations.
Highlights
Most of the counterions neutralizing the surface charge of a bilayer that contains ionic lipids reside within a thin layer parallel to the membrane plane
When the polyvalent ion concentration in solution increases to a point that they neutralize all the double stranded DNA (dsDNA) phosphate charges, they mediate attractive interactions between neighboring dsDNAs, inducing a process known as DNA condensation, whereby the dsDNA molecules condense into hexagonally packed double helices.[7]
Lipoplexes are spontaneously formed in aqueous solution upon bringing together dsDNA and cationic lipid bilayers into the same volume.[20,24,25]
Summary
The electric eld around linear, quasi one-dimensional (1D) macroions, e.g., DNA, is qualitatively different from the one generated by 2D macroions such as ionic lipid membranes. A striking example of this behavior, as well as a dramatic demonstration of counterion release, is the formation of cationic lipid–DNA complexes These complexes, known as lipoplexes,[17,18,19,20] were originally designed and are currently used as gene delivery vectors.[21,22,23] Lipoplexes are spontaneously formed in aqueous solution upon bringing together dsDNA and cationic lipid bilayers into the same volume.[20,24,25] As a concrete example, consider the mixing of two similar salt (e.g., 0.1 M NaCl) solutions: one containing dsDNA molecules, totaling NDÀ phosphate charges (balanced by the same number of sodium ions), and the other containing binary lipid vesicles composed of. That in the absence of DNA, these honeycomblike structures are rather unstable, owing to strong electrostatic repulsion between the charged lipid headgroups
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
