Gabriel S. Longo

Molecular theory of weak polyelectrolyte thin films

In this work, we extend the recently developed Molecular Theory of Weak Polyelectrolyte Gels to study hydrogel films. This approach explicitly accounts for all of the physicochemical interactions determining the thermodynamic equilibrium of these films and it incorporates molecular details of the polymer network. In particular, we applied this theoretical framework to investigate the response of a thin film of cross-linked hydrophilic polyacid chains to variations in external stimuli such as pH, salt concentration and applied electric potential. Swelling of the polyacid gel film is a continuous but sharp transition that occurs in a narrow range of bulk pH, around the pKa of the acid monomers. The width of this transition range depends on the salt concentration. The gel swells if the bulk pH is larger than the pKa of the monomers and it collapses otherwise. Swelling, however, is not due to a high degree of dissociation in the network, since the swollen gel can have very low degree of electric charge, but the result of the complex balance between the acid–base equilibrium, the gel molecular organization, and the resulting electrostatic interactions. The region close to the surface (up to a few nanometres-thick), the center of the gel, and the interface between the film and the solution have different chemical compositions, which are each different from that of the bulk solution in equilibrium with the film. In particular, the pH in all these regions can be controlled by changing the bulk pH and salt concentration. In addition, there is a gradient of pH going from the solution inside the film, whose magnitude can be tuned by varying bulk pH and salt concentration. In the region near the surface, both the pH and total charge density can be controlled by applying an electric potential. The thin film behaves as an electric insulating material. We calculated the potential of mean force for the insertion of charged nanoparticles inside the hydrogel film. Depending on the electric charge and size of the nanoparticle, there can be an attractive well or a repulsive barrier of several kBT for the nanoparticle to enter the gel from the solution. These findings are relevant in the design of a variety of functional devices using hydrogel films.

pH-controlled nanoaggregation in amphiphilic polymer co-networks.

Domain formation and control in pH-responsive amphiphilic polymer co-networks are studied theoretically. Two different molecular architectures of the polymer network are considered, depending on whether the pH-sensitive motif is borne by the hydrophobic or the hydrophilic monomer. When the hydrophobic polymer contains acidic groups, such chains form nanometric aggregates at acidic conditions, but they are found in a swollen state at alkaline pH. At intermediate pH, the nanoaggregation behavior of the hydrophobic polymer depends critically on the environment salt concentration. Moreover, our results indicate the presence of microphase separation into domains of swollen and aggregated hydrophobic chains. If the hydrophilic polymer is the ionizable component of the network, the nanoaggregation of hydrophobic monomers is weakly dependent on the pH and salt concentration, and except at very low volume fraction, the aggregate is the most probable conformation of the network in the entire range of pH and salt concentration studied. The two different hydrogels display quantitatively similar swelling transition and apparent pKa, but at the nanoscale, their behavior is qualitatively different. The spatial distribution of electric charge on the network as well as the local density of the different chemical species within the hydrogel can be controlled, as a function of pH and salt concentration, by the molecular architecture of the polymer network. These findings have relevance for applications in biomaterials and nanotechnology, in particular, in the design of oral delivery devices for the administration of hydrophobic drugs.

Calculating Partition Coefficients of Chain Anchors in Liquid-Ordered and Liquid-Disordered Phases

We calculate partition coefficients of various chain anchors in liquid-ordered and liquid-disordered phases utilizing a theoretical model of a bilayer membrane containing cholesterol, dipalmitoyl phosphatidylcholine, and dioleoylphosphatidylcholine. The partition coefficients are calculated as a function of chain length, degree of saturation, and temperature. Partitioning depends on the difference between the lipid environments of the coexisting phases in which the anchors are embedded. Consequently, the partition coefficient depends on the nature of the anchor, and on the relative compositions of the coexisting phases. We find that saturated anchors prefer the denser liquid-ordered phase, and that the fraction of anchors in the liquid-ordered phase increases with increasing degree of saturation of the anchors. The partition coefficient also depends upon the location of the double bonds. Anchors with double bonds closer to the middle of the chain have a greater effect on partitioning than those near the end. Doubling the number of saturated chains increases the partitioning into the liquid-ordered phase for tails that are nearly as long or longer than those comprising the bilayer. Partitioning of such chains increases with decreasing temperature, indicating that energy considerations dominate entropic ones. In contrast, partitioning of shorter chains increases with increasing temperature, indicating that entropic considerations dominate.

Stability and Liquid-Liquid Phase Separation in Mixed Saturated Lipid Bilayers

The phase stability of a fluid lipid bilayer composed of a mixture of DC(18)PC, (DSPC), and a shorter DCn(s) PC, with n(s) from 8 to 17, has been studied using a self-consistent field theory that explicitly includes molecular details and configurational properties of the lipid molecules. Phase separation between two liquid phases was found when there was a sufficient mismatch between the hydrophobic thicknesses of the two bilayers composed entirely of one component or the other. This occurs when n(s) <or = 12 and there is a sufficient concentration of the shorter lipid. The mixture separates into a thin bilayer depleted of DSPC and a thick bilayer enriched in DSPC. Even when there is no phase separation, as in the cases when there is either insufficient concentration of a sufficiently short lipid or any concentration of a lipid with n(s) > 12, we observe that the effect of the shorter lipid is to increase the susceptibility of the system to fluctuations in the concentration. This is of interest, given that a common motif for the anchoring of proteins to the plasma membrane is via a myristoyl chain, that is, one with 14 carbons.

Ligand - Receptor interactions between surfaces: The role of binary polymer spacers

The interactions between a receptor-modified planar surface and a surface grafted with a bimodal polymer layer, where one of the polymer species is ligand functionalized, are studied using a molecular theory. The effects of changing the binding energy of the ligand-receptor pair, the polymer surface coverage, the composition, and molecular weight of both the unfunctionalized and ligand functionalized polymers on the interactions between the surfaces are investigated. Our findings show that bridging exists between the surfaces including when the molecular weight of the ligand-bearing polymer is smaller than that of the unfunctionalized polymer, even though the ligand is initially buried within the polymer layer. The distance at which the surfaces bind depends only on the molecular weight of the ligand-modified polymer, while the strength of the interaction at a given surface separation can be tuned by changing the molecular weight of the polymers, the total polymer surface coverage, and the fraction of ligated polymers. The composition of the bimodal layer alters the structure of the polymer layer, thereby influencing the strength of the steric repulsions between the surfaces. Our theoretical results show good agreement with experimental data. The present theoretical study can be used as guidelines for the design of surfaces with tailored abilities for tunning the binding strength and surface-ligand separation distances for polymer-grafted surfaces bearing specific targeting ligands.

Non-monotonic swelling of surface grafted hydrogels induced by pH and/or salt concentration

We use a molecular theory to study the thermodynamics of a weak-polyacid hydrogel film that is chemically grafted to a solid surface. We investigate the response of the material to changes in the pH and salt concentration of the buffer solution. Our results show that the pH-triggered swelling of the hydrogel film has a non-monotonic dependence on the acidity of the bath solution. At most salt concentrations, the thickness of the hydrogel film presents a maximum when the pH of the solution is increased from acidic values. The quantitative details of such swelling behavior, which is not observed when the film is physically deposited on the surface, depend on the molecular architecture of the polymer network. This swelling-deswelling transition is the consequence of the complex interplay between the chemical free energy (acid-base equilibrium), the electrostatic repulsions between charged monomers, which are both modulated by the absorption of ions, and the ability of the polymer network to regulate charge and control its volume (molecular organization). In the absence of such competition, for example, for high salt concentrations, the film swells monotonically with increasing pH. A deswelling-swelling transition is similarly predicted as a function of the salt concentration at intermediate pH values. This reentrant behavior, which is due to the coupling between charge regulation and the two opposing effects triggered by salt concentration (screening electrostatic interactions and charging/discharging the acid groups), is similar to that found in end-grafted weak polyelectrolyte layers. Understanding how to control the response of the material to different stimuli, in terms of its molecular structure and local chemical composition, can help the targeted design of applications with extended functionality. We describe the response of the material to an applied pressure and an electric potential. We present profiles that outline the local chemical composition of the hydrogel, which can be useful information when designing applications that pursue or require the absorption of biomolecules or pH-sensitive molecules within different regions of the film.

New insight into the electrochemical desorption of alkanethiol SAMs on gold.

A combination of Polarization Modulation Infrared Reflection Absorption Spectroscopy (PMIRRAS) under electrochemical control, Electrochemical Scanning Tunneling Microscopy (ECSTM) and Molecular Dynamics (MD) simulations has been used to shed light on the reductive desorption process of dodecanethiol (C12) and octadecanethiol (C18) SAMs on gold in aqueous electrolytes. Experimental PMIRRAS, ECSTM and MD simulations data for C12 desorption are consistent with formation of randomly distributed micellar aggregates stabilized by Na(+) ions, coexisting with a lying-down phase of molecules. The analysis of pit and Au island coverage before and after desorption is consistent with the thiolate-Au adatoms models. On the other hand, PMIRRAS and MD data for C18 indicate that the desorbed alkanethiolates adopt a Na(+) ion-stabilized bilayer of interdigitated alkanethiolates, with no evidence of lying down molecules. MD simulations also show that both the degree of order and tilt angle of the desorbed alkanethiolates change with the surface charge on the metal, going from bilayers to micelles. These results demonstrate the complexity of the alkanethiol desorption in the presence of water and the fact that chain length and counterions play a key role in a complex structure.

Adsorption and protonation of peptides and proteins in pH responsive gels

To describe the non-trivial features of the equilibrium protonation and physical adsorption of peptides/proteins in pH-responsive hydrogels, we summarize our recent theoretical work on the subject. In these systems, molecular confinement in nanometer-sized environments modifies the balance between chemical state, physical interactions and molecular organization, which results in a behavior that is qualitatively different from what is expected from assuming the bulk solution protonation. To enhance adsorption, the pH-dependent deprotonation curves of all amino acids of adsorbed proteins are adequately shifted and deformed, which depends, in a complex fashion, on the specific amino acid. This possibility of modifying different acid–base equilibriums gives the adsorbed protein degrees of freedom to regulate charge and enhance electrostatic attractions under a wide range of experimental conditions. Protein adsorption modifies the microenvironment inside the hydrogel, particularly the gel pH. As a result, the state of protonation of the network is different before and after adsorption. The physicochemical considerations described in this review can be useful in the design of functional materials involving protein adsorption.

Equilibrium adsorption of hexahistidine on pH-responsive hydrogel nanofilms.

We present a molecular theory to study the adsorption of different species within pH-sensitive hydrogel nanofilms. The theoretical framework allows for a molecular-level description of all the components of the system, and it explicitly accounts for the acid-base equilibrium. We concentrate on the adsorption of hexahistidine, one of the most widely used tags in bio-related systems, particularly in chromatography of proteins. The adsorption of hexahistidine within a grafted polyacid hydrogel film shows a nonmonotonic dependence on the solution pH. Depending on the salt concentration, the density of the polymer network, and the bulk concentration of peptide, substantial adsorption is predicted in the intermediate pH range where both the network and the amino acids are charged. To enhance the electrostatic attractions, the acid-base equilibrium of adsorbed hexahistidine is shifted significantly, increasing the degree of charge of the residues as compared to the bulk solution. Such a shift depends critically on the conditions of the environment at the nanoscale. At the same time, the degree of dissociation of the network becomes that of the isolated acid group in a dilute solution, which means that the network is considerably more charged than when there is no adsorbate molecules. This work provides fundamental information on the physical chemistry behind the adsorption behavior and the response of the hydrogel film. This information can be useful in designing new materials for the purification or separation/immobilization of histidine-tagged proteins.

Stability and phase separation in mixed self-assembled monolayers.

Recent single molecule experiments rely on the self-assembly of binary mixtures of molecules with very different properties in a stable monolayer, in order to probe the characteristics of the interspersed molecule of interest in a controlled environment. However, not all efforts at coassembly have been successful. To study systematically the behavior of such systems, we derive the free energy of multicomponent systems of rods with configurational degrees of freedom, localized on a surface, starting from a generalized van der Waals description. The molecular parameters are determined by geometrical factors of the molecules and by their pairwise van der Waals interactions computed using molecular mechanics. Applying the model to two experimental situations, we are able to use the stability analysis of the respective mixtures to explain why coassembly was successful in one set of experiments (carotene and alkanethiol) and not in another (benzenethiols and alkanethiol). We outline general guidelines for suitable choices of molecules to achieve coassembly.