Wu Y, Shapiro L, Honig B, Ben-Shaul A.
Theory and simulations of receptor binding in inter-cell adhesion and junction formation. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. 2013;245.
Harries D, May S, Ben-Shaul A.
Counterion release in membrane-biopolymer interactions. SOFT MATTER. 2013;9 :9268-9284.
AbstractWhen 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.
2013.dhsmabs.soft_matter.pdf Ben-Shaul A.
Entropy, Energy, and Bending of DNA in Viral Capsids. BIOPHYSICAL JOURNAL. 2013;104 :L15-L17.
AbstractInspired by novel single-molecule and bulk solution measurements, the physics underlying the forces and pressures involved in DNA packaging into bacteriophage capsids became the focus of numerous recent theoretical models. These fall into two general categories: Continuum-elastic theories (CT), and simulation studies-mostly of the molecular dynamics (MD) genre. Both types of models account for the dependence of the force, and hence the packaging free energy (Delta F), on the loaded DNA length, but differ markedly in interpreting their origin. While DNA confinement entropy is a dominant contribution to DF in the MD simulations, in the CT theories this role is fulfilled by interstrand repulsion, and there is no explicit entropy term. The goal of this letter is to resolve this apparent contradiction, elucidate the origin of the entropic term in the MD simulations, and point out its tacit presence in the CT treatments.
2013.abs_.bj_.wrev_.pdf Wu Y, Honig B, Ben-Shaul A.
Theory and Simulations of Adhesion Receptor Dimerization on Membrane Surfaces. BIOPHYSICAL JOURNAL. 2013;104 :1221-1229.
AbstractThe equilibrium constants of trans and cis dimerization of membrane bound (2D) and freely moving (3D) adhesion receptors are expressed and compared using elementary statistical-thermodynamics. Both processes are mediated by the binding of extracellular subdomains whose range of motion in the 2D environment is reduced upon dimerization, defining a thin reaction shell where dimer formation and dissociation take place. We show that the ratio between the 2D and 3D equilibrium constants can be expressed as a product of individual factors describing, respectively, the spatial ranges of motions of the adhesive domains, and their rotational freedom within the reaction shell. The results predicted by the theory are compared to those obtained from a novel, to our knowledge, dynamical simulations methodology, whereby pairs of receptors perform realistic translational, internal, and rotational motions in 2D and 3D. We use cadherins as our model system. The theory and simulations explain how the strength of cis and trans interactions of adhesive receptors are affected both by their presence in the constrained intermembrane space and by the 2D environment of membrane surfaces. Our work provides fundamental insights as to the mechanism of lateral clustering of adhesion receptors after cell-cell contact and, more generally, to the formation of lateral microclusters of proteins on cell surfaces.
2013.ywbhabs.bj_.pdf