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I Szleifer

Publications and source records attributed to I Szleifer.

16 recordsLinked to original sources
PubMed2006

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.

Journal Article↗
PubMed2006

Controlled release of proteins from polymer-modified surfaces.

The ability to control the rate of adsorption and desorption of proteins from surfaces is studied by using a molecular theory. We show how changing the chemical structure and charge of short linear and branched grafted polymers to an electrode surface can be used to promote fast adsorption of charged proteins on a time scale of seconds and control the desorption in a time scale ranging from milliseconds to hours. The optimal controlled release is found from the interplay of electrostatic attractions at short distances from the surface and the proper electrostatic and steric repulsive barrier at distances from the surfaces larger than the proteins' size. The implications of our results to the design of controlled-release devices is discussed.

Adsorption↗
PubMed2006

Phase diagram of a ternary mixture of cholesterol and saturated and unsaturated lipids calculated from a microscopic model.

We employ a molecular model to study a ternary mixture of saturated lipid, with tails of 16 carbons, a monounsaturated lipid with tails of 18 carbons, and cholesterol. The model, solved within mean-field theory, produces several forms of phase diagrams depending upon the relative strengths of interactions, but only one that shows the coexistence of two liquid phases observed in experiment. The lipids in the phase rich in cholesterol are more ordered than those in the other. The binary cholesterol, saturated lipid system also exhibits liquid, liquid coexistence.

Cholesterol↗
PubMed2006

Cluster structure and corralling effect driven by interaction mismatch in two dimensional mixtures.

The formation of clusters with crystal-like order in two dimensions is studied using Monte Carlo simulations. We find that the necessary conditions to induce the formation of clusters of one component is to add a second component that has a larger size and that has a long-range soft repulsive interaction with its own kind but not with the other one. The clusters of the small particles are found to be surrounded by a network of quasi-one-dimensional arrangements of the larger particles. The degree of order of the clusters is found to depend on the concentration of the larger particles. The findings explain recent experimental observations on lipid-poloxamer mixtures and they provide guidelines for how to form ordered clusters of nanoparticles in two dimensions.

Journal Article↗
PubMed2005

Ligand-receptor interactions in tethered polymer layers.

The binding of small proteins to ligands that are attached to the free ends of polymers tethered to a planar surface is studied using a molecular theory. The effects of changing the intrinsic binding equilibrium constant of the ligand-receptor pair, the polymer surface coverage, the polymer molecular weight, and the protein size are studied. The results are also compared with the case where ligands are directly attached to the surface without a polymer acting as a spacer. We found that within the biological range of binding constants the protein adsorption is enhanced by the presence of the polymer spacers. There is always an optimal surface coverage for which ligand-receptor binding is a maximum. This maximum increases as the binding energy and/or the polymer molecular weight increase. The presence of the maximum is due to the ability of the polymer-bound proteins to form a thick layer by dispersing the ligands in space to optimize binding and minimize lateral repulsions. The fraction of bound receptors is unity for a very small surface coverage of ligands. The very sharp decrease in the fraction of bound ligand-receptor pairs with surface coverage depends on the polymer spacer chain length. We found that the binding of proteins is reduced as the size of the protein increases. The orientation of the bound proteins can be manipulated by proper choice of the grafted layer conditions. At high polymer surface coverage the bound proteins are predominantly perpendicular to the surface, while at low surface coverage there is a more random distribution of orientations. To avoid nonspecific adsorption on the surface, we studied the case where the surface is covered by a mixture of a relatively high molecular weight polymer with a ligand attached to its free end and a low molecular weight polymer without ligand. These systems present a maximum in the binding of proteins, which is of the same magnitude as when only the long polymer-ligand is present. Moreover, when the total surface coverage in the mixed layers of polymers is high enough, nonspecific adsorption of the proteins on the surface is suppressed. The use of the presented theoretical results for the design of surface modifiers with tailored abilities for specific binding of proteins and optimal nonfouling capabilities is discussed.

Adsorption↗
PubMed2005

Phase separation of saturated and mono-unsaturated lipids as determined from a microscopic model.

A molecular model is proposed of a bilayer consisting of fully saturated dipalmitoylphosphatidylcholine (DPPC) and mono-unsaturated dioleoylphosphatidylcholine (DOPC). The model not only encompasses the constant density within the hydrophobic core of the bilayer, but also the tendency of chain segments to align. It is solved within self-consistent field theory. A model bilayer of DPPC undergoes a main-chain transition to a gel phase, while a bilayer of DOPC does not do so above zero degrees centigrade because of the double bond which disrupts order. We examine structural and thermodynamic properties of these membranes and find our results in reasonable accord with experiment. In particular, order-parameter profiles are in good agreement with NMR experiments. A phase diagram is obtained for mixtures of these lipids in a membrane at zero tension. The system undergoes phase separation below the main-chain transition temperature of the saturated lipid. Extensions to the ternary DPPC, DOPC, and cholesterol system are outlined.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2004

Competitive adsorption of model charged proteins: the effect of total charge and charge distribution.

The adsorption of mixtures of charged proteins on charged surfaces is studied using a molecular theory. The theory explicitly treats each of the molecular species in the system. The mixtures treated in this work are composed by two types of proteins, dissociated monovalent salt and solvent. The intermolecular and surface interactions include electrostatic, van der Waals and excluded volume. The theory is more general than the Poisson-Boltzmann approach since the size and shape of all the molecular components are explicitly treated. The studies presented in this work concentrate on the differences in competitive adsorption when the proteins in the mixtures differ in their total charge or in the spatial distribution of the charges within the proteins. In the cases of mixtures that differ in the number of charges it is found, as expected, that the particles with the larger charge adsorb in excess. The ratio of adsorbed proteins can vary by 3-5 orders of magnitude by varying the bulk salt concentration from 1 to 100 mM. This is the result of an increase on the adsorption of the proteins with larger charge and an even stronger decrease on the adsorption of the less charged particles. The simple model systems studied provide guidelines on how to separate charge ladder proteins and proteins with different charge distributions. In the case of proteins with the same total charge but different charge distribution, it is found that the partition of the proteins depends upon the bulk composition. However, in general the particles with the highest localized charge tend to adsorb more on the surfaces. The proteins are adsorbed in one or more layers. The structure of the second adsorbed layer is determined mostly by the bulk properties of the solution. In all cases it is found that in the range of salt concentrations studied the number of adsorbed ions from the salt is very large. This is due to competitive adsorption with the proteins and their very low bulk concentration compared to the salt. The limitations of the theory and directions for improvement of the approach as well as the model for the proteins are discussed.

Adsorption↗
PubMed2001

Kinetics and thermodynamics of protein adsorption: a generalized molecular theoretical approach.

The thermodynamics and kinetics of protein adsorption are studied using a molecular theoretical approach. The cases studied include competitive adsorption from mixtures and the effect of conformational changes upon adsorption. The kinetic theory is based on a generalized diffusion equation in which the driving force for motion is the gradient of chemical potentials of the proteins. The time-dependent chemical potentials, as well as the equilibrium behavior of the system, are obtained using a molecular mean-field theory. The theory provides, within the same theoretical formulation, the diffusion and the kinetic (activated) controlled regimes. By separation of ideal and nonideal contributions to the chemical potential, the equation of motion shows a purely diffusive part and the motion of the particles in the potential of mean force resulting from the intermolecular interactions. The theory enables the calculation of the time-dependent surface coverage of proteins, the dynamic surface tension, and the structure of the adsorbed layer in contact with the approaching proteins. For the case of competitive adsorption from a solution containing a mixture of large and small proteins, a variety of different adsorption patterns are observed depending upon the bulk composition, the strength of the interaction between the particles, and the surface and size of the proteins. It is found that the experimentally observed Vroman sequence is predicted in the case that the bulk solution is at a composition with an excess of the small protein, and that the interaction between the large protein and the surface is much larger than that of the smaller protein. The effect of surface conformational changes of the adsorbed proteins in the time-dependent adsorption is studied in detail. The theory predicts regimes of constant density and dynamic surface tension that are long lived but are only intermediates before the final approach to equilibrium. The implications of the findings to the interpretation of experimental observations is discussed.

Adsorption↗
PubMed2000

Prevention of protein adsorption by flexible and rigid chain molecules.

The ability of tethered polymer layers to reduce the non-specific adsorption of proteins is studied using a molecular theory. The protein adsorption isotherms are calculated for flexible and rigid molecules as well as for mixtures. It is found, in agreement with earlier predictions, that flexible polymers are more effective in preventing protein adsorption. The interactions of the polymer with the surface are shown to be very important in determining the ability of the polymer layer to reduce the adsorption of proteins. Further, it is found that one can tune the adsorption of a certain protein conformation by changing the interactions between the surface and the polymer segments or the composition in the case of mixtures. It is found that the optimal layers to obtain large reduction of protein adsorption and availability of functional groups for binding are obtained by using mixtures of flexible and rod-like molecules. The role of the polymer-surface interactions is shown to be different for the kinetic control of protein adsorption as compared to thermodynamic control. The application of the findings as guidelines for the molecular design of biocompatible materials is discussed.

Journal Article↗
PubMed2000

Kinetic and thermodynamic control of protein adsorption.

Control of nonspecific protein adsorption is very important for the design of biocompatible and biomimetic materials as well as drug carriers. Grafted polymer layers can be used to prevent protein adsorption. We have studied the molecular factors that determine the equilibrium and kinetic control of protein adsorption by grafted polymer layers. We find that polymers that are not attracted to the surface are very effective for kinetic control but not very good for equilibrium reduction of protein adsorption. Polymers with attractions to the surface show exactly the opposite behavior. The implications for molecular design of biocompatible materials also are discussed in this paper.

Adsorption↗
PubMed1998

Spontaneous liposome formation induced by grafted poly(ethylene oxide) layers: theoretical prediction and experimental verification.

Spontaneous liposome formation is predicted in binary mixtures of fluid phase phospholipids and poly(n)ethylene oxide (PEO)-bearing lipids by using single chain mean field theory. The range of stability of the spontaneous liposomes is determined as a function of percentage of PEO-conjugated lipids and polymer molecular weight. These predictions were tested by using cast films of 1, 2-diacyl-sn-glycerophosphocholines (e.g., egg L-alpha-lecithin, 1, 2-dimyristoyl-sn-glycero-3-phosphocholine, 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine, and 1, 2-distearoyl-sn-glycero-3-phosphocholine) and 1, 2-dipalmitoyl-sn-glycerophosphatidylethanolamine-PEO conjugates (i.e. , 1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxypoly(e thylen e glycol)2000]carboxamide and 1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxypoly(e thylen e oxide)5000]carboxamide) that were hydrated above their gel-liquid crystal phase transition temperatures. Particle sizes of the resulting dispersions, analyzed by quasielastic light scattering, solute retention, 31P NMR, and freeze-fracture electron microscopy measurements, confirmed the single chain mean field predictions. These data indicate that thermodynamically stable, unilamellar liposomes are formed spontaneously by simple hydration of fluid phase phospholipid bilayer films containing low molar ratios of PEO-based amphiphiles. They further suggest that the equilibrium size and colloidal properties of fluid phase, PEO-modified liposomes can be predicted by using this theoretical approach. The implication of these results on the design and processing of sterically stabilized liposomes used in drug delivery applications also is described.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

Protein adsorption on surfaces with grafted polymers: a theoretical approach.

A general theoretical framework for studying the adsorption of protein molecules on surfaces with grafted polymers is presented. The approach is a generalization of the single-chain mean-field theory, in which the grafted polymer-protein-solvent layer is assumed to be inhomogeneous in the direction perpendicular to the grafting surface. The theory enables the calculation of the adsorption isotherms of the protein as a function of the surface coverage of grafted polymers, concentration of protein in bulk, and type of solvent molecules. The potentials of mean force of the protein with the surface are calculated as a function of polymer surface coverage and amount of protein adsorbed. The theory is applied to model lysozyme on surfaces with grafted polyethylene oxide. The protein is modeled as spherical in solution, and it is assumed that the protein-polymer, protein-solvent, and polymer-solvent attractive interactions are all equal. Therefore, the interactions determining the structure of the layer (beyond the bare polymer-surface and protein-surface interactions) are purely repulsive. The bare surface-protein interaction is taken from atomistic calculations by Lee and Park. For surfaces that do not have preferential attractions with the grafted polymer segments, the adsorption isotherms of lysozyme are independent of the polymer length for chains with more than 50 ethylene oxide units. However, the potentials of mean force show strong variations with grafted polymer molecular weight. The competition between different conformations of the adsorbed protein is studied in detail. The adsorption isotherms change qualitatively for surfaces with attractive interactions with ethylene oxide monomers. The protein adsorption is a function of chain length--the longer the polymer the more effective it is in preventing protein adsorption. The structure of the layer and its deformation upon protein adsorption are very important in determining the adsorption isotherms and the potentials of mean force.

Adsorption↗
PubMed1984

Statistical thermodynamics of amphiphile chains in micelles.

The probability distribution of amphiphile chain conformations in micelles of different geometries is derived through maximization of their packing entropy. A lattice model, first suggested by Dill and Flory, is used to represent the possible chain conformations in the micellar core. The polar heads of the chains are assumed to be anchored to the micellar surface, with the other chain segments occupying all lattice sites in the interior of the micelle. This "volume-filling" requirement, the connectivity of the chains, and the geometry of the micelle define constraints on the possible probability distributions of chain conformations. The actual distribution is derived by maximizing the chain's entropy subject to these constraints; "reversals" of the chains back towards the micellar surface are explicitly included. Results are presented for amphiphiles organized in planar bilayers and in cylindrical and spherical micelles of different sizes. It is found that, for all three geometries, the bond order parameters decrease as a function of the bond distance from the polar head, in accordance with recent experimental data. The entropy differences associated with geometrical changes are shown to be significant, suggesting thereby the need to include curvature (environmental)-dependent "tail" contributions in statistical thermodynamic treatments of micellization.

Journal Article↗