Mark Uline - Academia.edu (original) (raw)

Papers by Mark Uline

Journal of the Mechanical Behavior of Biomedical Materials, 2015

Coronary artery bypass grafting (CABG) acutely disturbs the homeostatic state of the transplanted... more Coronary artery bypass grafting (CABG) acutely disturbs the homeostatic state of the transplanted vessel making retention of graft patency dependent on chronic remodeling processes. The time course and extent to which remodeling restores vessel homeostasis will depend, in part, on the nature and magnitude of the mechanical disturbances induced upon transplantation. In this investigation, biaxial mechanical testing and histology were performed on the porcine left anterior descending artery (LAD) and analogs of common autografts, including the internal thoracic artery (ITA), radial artery (RA), great saphenous vein (GSV) and lateral saphenous vein (LSV). Experimental data were used to quantify the parameters of a structure-based constitutive model enabling prediction of the acute vessel mechanical response pre-transplantation and under coronary loading conditions. A novel metric Ξ was developed to quantify mechanical differences between each graft vessel in situ and the LAD in situ, while a second metric Ω compares the graft vessels in situ to their state under coronary loading. The relative values of these metrics among candidate autograft sources are consistent with vessel-specific variations in CABG clinical success rates with the ITA as the superior and GSV the inferior graft choices based on mechanical performance. This approach can be used to evaluate other candidate tissues for grafting or to aid in the development of synthetic and tissue engineered alternatives.

Nature chemical biology, Jan 26, 2015

Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between di... more Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for enrichment in raft-like liquid-ordered phases; enrichment was driven by relief of lateral pressure upon anchor insertion and most likely affects the localization of lipidated proteins in general.

We calculate partition coe!cients of various chain anchorsin liquid-ordered and liquid- disordere... more We calculate partition coe!cients of various chain anchorsin liquid-ordered and liquid- disordered phases utilizing a theoretical model of a bilayer membrane containing cholesterol, di- palmitoylphophatidylcholine (DPPC), and dioleoylphosphatidylcholine (DOPC). The partition coe!cients are calculated as a function of chain length, degree of saturation, and temperature. Partitioning depends on the di"erence between the lipid environments of the coexisting phases in which the anchors are embedded. As a consequence the partition coe!cient depends not only upon the nature of the anchor, but also 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 coe!cient also depends upon the location of the double bonds. Anchors with double bonds closer to the middle of the chain have a ...

Physical Review Letters, 2007

For the superheated Lennard-Jones liquid, the free energy of forming a bubble with a given partic... more For the superheated Lennard-Jones liquid, the free energy of forming a bubble with a given particle number and volume is calculated using density-functional theory. As conjectured, a consequence of known properties of the critical cavity [S. N. Punnathanam and D. S. Corti, J. Chem. Phys. 119, 10 224 (2003), the free energy surface terminates at a locus of instability. These stability limits reside, however, unexpectedly close to the saddle point. A new picture of homogeneous bubble nucleation and growth emerges from our study, being more appropriately described as an "activated instability."

The Journal of Chemical Physics, 2010

The free energy of forming a droplet and a bubble with a given particle number n and volume v wit... more The free energy of forming a droplet and a bubble with a given particle number n and volume v within the pure-component Lennard-Jones supercooled vapor and superheated liquid, respectively, are further explored using density-functional theory. Similar to what was found previously ͓M. J. Uline and D. S. Corti, Phys. Rev. Lett. 99, 076102 ͑2007͒; M. J. Uline and D. S. Corti, J. Chem. Phys. 129, 234507 ͑2008͔͒, the limits of stability again appear within both free energy surfaces evaluated at two other metastability conditions, one closer to the binodal and one closer to the spinodal. Furthermore, an ad hoc bond connectivity criterion is also applied in an attempt, however approximately, to eliminate certain configurational redundancies that arise from the chosen droplet and bubble definitions. What results are free energy surfaces describing the formation of equilibrium embryos that should be an improved representation of the fluctuations that are relevant to those nonequilibrium embryos seen in an actual nucleation event. Finally, we discuss in some detail the use of the ͑n , v͒ reaction coordinate within the framework of an equilibrium-based theory and its relation to other descriptions of nucleation.

The Journal of Chemical Physics, 2008

For the pure-component supercooled Lennard-Jones vapor, the free energy of forming a droplet with... more For the pure-component supercooled Lennard-Jones vapor, the free energy of forming a droplet with a given particle number and volume is calculated using density-functional theory. In contrast to what was noted in previous studies, the free energy surface beyond the pseudosaddle point no longer exhibits a valley but rather channels the nuclei toward a locus of instabilities, initiating an unstable growth phase. Similar to a previous study of bubble formation in superheated liquids [M. J. Uline and D. S. Corti, Phys. Rev. Lett. 99, 076102 (2007)], a new picture of homogeneous droplet nucleation and growth emerges.

The Journal of Chemical Physics, 2008

We consider various ensemble averages within the molecular dynamics (MD) ensemble, corresponding ... more We consider various ensemble averages within the molecular dynamics (MD) ensemble, corresponding to those states sampled during a MD simulation in which the application of periodic boundary conditions imposes a constraint on the momentum of the center of mass. As noted by Shirts et al. [J. Chem. Phys. 125, 164102 (2006)] for an isolated system, we find that the principle of equipartition is not satisfied within such simulations, i.e., the total kinetic energy of the system is not shared equally among all the translational degrees of freedom. Nevertheless, we derive two different versions of Tolman's generalized equipartition theorem, one appropriate for the canonical ensemble and the other relevant to the microcanonical ensemble. In both cases, the breakdown of the principle of equipartition immediately follows from Tolman's result. The translational degrees of freedom are, however, still equivalent, being coupled to the same bulk property in an identical manner. We also show that the temperature of an isolated system is not directly proportional to the average of the total kinetic energy (in contrast to the direct proportionality that arises between the temperature of the external bath and the kinetic energy within the canonical ensemble). Consequently, the system temperature does not appear within Tolman's generalized equipartition theorem for the microcanonical ensemble (unlike the immediate appearance of the temperature of the external bath within the canonical ensemble). Both of these results serve to highlight the flaws in the argument put forth by Hertz [Ann. Phys. 33, 225 (1910); 33, 537 (1910)] for defining the entropy of an isolated system via the integral of the phase space volume. Only the Boltzmann-Planck entropy definition, which connects entropy to the integral of the phase space density, leads to the correct description of the properties of a finite, isolated system. We demonstrate that the use of the integral of the phase space volume leads to unphysical results, indicating that the property of adiabatic invariance has little to do with the behavior of small systems.

The Journal of Chemical Physics, 2008

Based on the approach of Gruhn and Monson [Phys. Rev. E 63, 061106 (2001)], we present a new meth... more Based on the approach of Gruhn and Monson [Phys. Rev. E 63, 061106 (2001)], we present a new method for deriving the collisions dynamics for particles that interact via discontinuous potentials. By invoking the conservation of the extended Hamiltonian, we generate molecular dynamics (MD) algorithms for simulating the hard-sphere and square-well fluids within the isothermal-isobaric (NpT) ensemble. Consistent with the recent rigorous reformulation of the NpT ensemble partition function, the equations of motion impose a constant external pressure via the introduction of a shell particle of known mass [M. J. Uline and D. S. Corti, J. Chem. Phys. 123, 164101 (2005); 123, 164102 (2005)], which serves to define uniquely the volume of the system. The particles are also connected to a temperature reservoir through the use of a chain of Nose-Hoover thermostats, the properties of which are not affected by a hard-sphere or square-well collision. By using the Liouville operator formalism and the Trotter expansion theorem to integrate the equations of motion, the update of the thermostat variables can be decoupled from the update of the positions of the particles and the momentum changes upon a collision. Hence, once the appropriate collision dynamics for the isobaric-isenthalpic (NpH) equations of motion is known, the adaptation of the algorithm to the NpT ensemble is straightforward. Results of MD simulations for the pure component square-well fluid are presented and serve to validate our algorithm. Finally, since the mass of the shell particle is known, the system itself, and not a piston of arbitrary mass, controls the time scales for internal pressure and volume fluctuations. We therefore consider the influence of the shell particle algorithm on the dynamics of the square-well fluid.

Journal of Chemical Education, 2006

ABSTRACT

Faraday Discussions, 2013

Using microscopic molecular theory, we determine the bending and saddle-splay constants of three-... more Using microscopic molecular theory, we determine the bending and saddle-splay constants of three-component lipid bilayers. The membrane contains cholesterol, dipalmitoyl-phosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC) and the predictions of the theory have been shown to qualitatively reproduce phase diagrams of giant unilamellar vesicles (GUVs) of the same three components. The bending and saddle-splay constants were calculated for the gel, liquid-ordered (lo) and liquid-disordered (ld) phases. By proper expansion of the free energy, the molecular theory enables us to determine the effects of the mode of membrane bending deformation on the value of the elastic constants for different phases. In particular, we refer to the ability of the molecules to arrange the composition between the two monolayers upon deformation. The bending and saddle-splay constants obtained from the free energy expansion can be expressed in terms of moments of the local lateral pressures and their derivatives, all evaluated for a symmetric planar bilayer. The effect of blocked vs. free exchange of lipids across the two monolayers on the values of the bending constant is as high as 50 k(B)Tin the ld phase to as high as 200 k(B)T in the lo phase. These results show that one must strongly consider the mode of deformation in determining the mechanical properties of lipid bilayers. We discuss how the different contributions to the lateral pressures affect the values of the elastic constants, including the effects of the cholesterol concentration and temperature on the membrane elastic constants. We also calculate the equilibrium binding concentrations of lipid tail anchors as a function of membrane curvature by explicitly determining the chemical potential difference of species across a curved bilayer. Our results are in excellent agreement with recent experimental results.

Biophysical Journal, 2010

Using a combination of all-atom and coarse-grained molecular dynamics simulations to interpret a ... more Using a combination of all-atom and coarse-grained molecular dynamics simulations to interpret a range of x-ray scattering experiments, we aim to understand the role of membrane deformation in the action of the Parkinson's Disease protein, a-Synuclein. Our simulation results have led to the hypothesis that aS flattens curved membranes by screening the repulsive interactions between negatively charged, acidic headgroups, thereby reducing the effective area per headgroup and relieving the inherent positive curvature of the lipids on the outer leaflet of synaptic vesicles. We hope to address the question of whether aS influences a membrane's mechanical properties as a route to evaluating this hypothesis. Additionally, we aim to understand the role of aS in recruiting sub-domains of positively charged lipids. A second, smaller peptide (the CRAC motif from gp41) is also studied in an effort to build the computational tools necessary for matching the x-ray data that is used for calculating a membrane's material properties.

Biophysical Journal, 2010

X-ray scattering is a promising tool with which to characterize systems of solidsupported membran... more X-ray scattering is a promising tool with which to characterize systems of solidsupported membranes. There are many different scattering techniques used in the characterization, but all suffer from a necessarily low electron density contrast between the membrane and the water medium in which it must exist. Labeling membranes with a high-contrast scatterer such as gold is a promising avenue to solve this problem. In this work, silicon-supported membranes of 1,2dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were prepared by both standard Langmuir-Blodgett deposition and fusion of vesicles onto the substrate surface. Membranes are characterized using specular x-ray reflectometry, and modeled to fit physical systems. One percent by count 1,2-dipalmitoyl-sn-glycero-phosphoethanolamine (DPPE) with a gold tag attached was then added to both systems. Gold labeled membranes were then characterized and modeled. The effect of gold labeling is shown to characteristically change the membrane density profile in addition to enhancing density contrast between the membrane and the water medium. We created two-dimensional (2D) assemblies of tobacco mosaic viruses (TMVs) and characterized their structures using Atomic Force Microscopy (AFM) and X-ray scattering. The TMVs were adsorbed on an oppositely charged, fluid lipid monolayer supported by a solid substrate and submerged in a buffer solution. The lipid monolayer confined the viral particles within a plane, while providing them with lateral mobility so that overall the TMV assembly behaved like a 2D liquid. The inter-particle interaction is controlled by the chemical condition in the buffer. The degree of structural orders observed varied, depending on both the inter-particle interaction and the lateral mobility of the particles. Quantitative analysis of the X-ray scattering data provides information on the nature of the interaction between TMVs as well as possible membrane deformation due to the contact with TMVs. This study provides the proof-of-concept that X-ray scattering may be used to study the structure of membrane associated proteins in substrate-supported single bilayer under near-native conditions.

Biophysical Journal, 2011

Pulmonary surfactant (PS) is a surface active lipoproteic material produced by type II cells at t... more Pulmonary surfactant (PS) is a surface active lipoproteic material produced by type II cells at the alveoli. This material forms a unique air-liquid interface lining the alveolar surface that reduces surface tension close to 0mN/m, maintaining lung volumes and alveolar homeostasis at the end of expiration. The particular lipid composition of PS suggests that mono-and bilayer-based structures should exhibit lateral phase segregation at physiological temperatures. This work on Native Pulmonary Surfactant Membranes (NPSM), directly isolated from broncho-alveolar lavages of wild-type mice show that a detailed lipid compositional study is crucial to understand the structure and biophysical function of these complex mixtures. Using different microscopy techniques, we have managed to analyze, in detail at the micro-and nano-scale, qualitative and quantitatively the whole native interfacial film responsible for breathing in mice. First, it was performed a study of the lipid phase segregation pattern on free-standing spherical and in planar solidsupported bilayers. Then, the phase behavior was investigated in planar solid-supported and in in-situ air-liquid monolayers. We found close correspondence in shape, size, height, area coverage and lipid phase of the domains between bilayers and monolayers. Contrary to what has been published until now. Particularly with monolayers, the quantification of the order among the different coexisting lipid phases indicates that the segregated rounded domains within a percolated larger area are more fluid. The phase segregation pattern remains until physiological relevant respiratory surface pressures, where we found non-homogeneous nanostructure serving as a platform for a highly corrugated-like collapsed structures, that grow size-and heightwise, arising from the more fluid phases. This last finding opens a new way to explore the pulmonary surfactant interfacial films, closer to materials science, which could help to understand such a basic and important topic; the respiration in mammals.

Biophysical Journal, 2010

We calculate partition coefficients of various chain anchors in liquid-ordered and liquid-disorde... more 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.

Langmuir, 2011

Charge regulation in polyacid monolayers attached at one end to a planar surface is studied theor... more Charge regulation in polyacid monolayers attached at one end to a planar surface is studied theoretically. The polyacid layers are designed to mimic single-stranded DNA monolayers. The effects of the local pH and salt concentration on the protonation states of the polyacid layer are studied using a molecular mean-field theory that includes a microscopic description of the conformations of the polyacid molecule along with electrostatic interactions, acid-base equilibrium, and excluded volume interactions. We predict that, in the case of a monovalent salt, NaCl, the amount of proton binding increases dramatically for high surface coverage of polyacid and low bulk salt concentration. When the polyelectrolyte is almost completely charge neutralized by bound protons, there is an expulsion of sodium from the layer. We show that the degree of protonation can go all the way from 0% to 100% when the bulk pH is kept fixed at 7 by changing the surface coverage of polyacid and the bulk salt concentration. The effects of increasing protonation and the expulsion of the cations from the monolayer are reduced when sodium ions are replaced by divalent magnesium ions. Our theoretical results concur with X-ray photoelectron spectroscopy studies of ssDNA monolayers on gold.

Journal of the Mechanical Behavior of Biomedical Materials, 2015

Coronary artery bypass grafting (CABG) acutely disturbs the homeostatic state of the transplanted... more Coronary artery bypass grafting (CABG) acutely disturbs the homeostatic state of the transplanted vessel making retention of graft patency dependent on chronic remodeling processes. The time course and extent to which remodeling restores vessel homeostasis will depend, in part, on the nature and magnitude of the mechanical disturbances induced upon transplantation. In this investigation, biaxial mechanical testing and histology were performed on the porcine left anterior descending artery (LAD) and analogs of common autografts, including the internal thoracic artery (ITA), radial artery (RA), great saphenous vein (GSV) and lateral saphenous vein (LSV). Experimental data were used to quantify the parameters of a structure-based constitutive model enabling prediction of the acute vessel mechanical response pre-transplantation and under coronary loading conditions. A novel metric Ξ was developed to quantify mechanical differences between each graft vessel in situ and the LAD in situ, while a second metric Ω compares the graft vessels in situ to their state under coronary loading. The relative values of these metrics among candidate autograft sources are consistent with vessel-specific variations in CABG clinical success rates with the ITA as the superior and GSV the inferior graft choices based on mechanical performance. This approach can be used to evaluate other candidate tissues for grafting or to aid in the development of synthetic and tissue engineered alternatives.

Nature chemical biology, Jan 26, 2015

Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between di... more Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for enrichment in raft-like liquid-ordered phases; enrichment was driven by relief of lateral pressure upon anchor insertion and most likely affects the localization of lipidated proteins in general.

We calculate partition coe!cients of various chain anchorsin liquid-ordered and liquid- disordere... more We calculate partition coe!cients of various chain anchorsin liquid-ordered and liquid- disordered phases utilizing a theoretical model of a bilayer membrane containing cholesterol, di- palmitoylphophatidylcholine (DPPC), and dioleoylphosphatidylcholine (DOPC). The partition coe!cients are calculated as a function of chain length, degree of saturation, and temperature. Partitioning depends on the di"erence between the lipid environments of the coexisting phases in which the anchors are embedded. As a consequence the partition coe!cient depends not only upon the nature of the anchor, but also 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 coe!cient also depends upon the location of the double bonds. Anchors with double bonds closer to the middle of the chain have a ...

Physical Review Letters, 2007

For the superheated Lennard-Jones liquid, the free energy of forming a bubble with a given partic... more For the superheated Lennard-Jones liquid, the free energy of forming a bubble with a given particle number and volume is calculated using density-functional theory. As conjectured, a consequence of known properties of the critical cavity [S. N. Punnathanam and D. S. Corti, J. Chem. Phys. 119, 10 224 (2003), the free energy surface terminates at a locus of instability. These stability limits reside, however, unexpectedly close to the saddle point. A new picture of homogeneous bubble nucleation and growth emerges from our study, being more appropriately described as an "activated instability."

The Journal of Chemical Physics, 2010

The free energy of forming a droplet and a bubble with a given particle number n and volume v wit... more The free energy of forming a droplet and a bubble with a given particle number n and volume v within the pure-component Lennard-Jones supercooled vapor and superheated liquid, respectively, are further explored using density-functional theory. Similar to what was found previously ͓M. J. Uline and D. S. Corti, Phys. Rev. Lett. 99, 076102 ͑2007͒; M. J. Uline and D. S. Corti, J. Chem. Phys. 129, 234507 ͑2008͔͒, the limits of stability again appear within both free energy surfaces evaluated at two other metastability conditions, one closer to the binodal and one closer to the spinodal. Furthermore, an ad hoc bond connectivity criterion is also applied in an attempt, however approximately, to eliminate certain configurational redundancies that arise from the chosen droplet and bubble definitions. What results are free energy surfaces describing the formation of equilibrium embryos that should be an improved representation of the fluctuations that are relevant to those nonequilibrium embryos seen in an actual nucleation event. Finally, we discuss in some detail the use of the ͑n , v͒ reaction coordinate within the framework of an equilibrium-based theory and its relation to other descriptions of nucleation.

The Journal of Chemical Physics, 2008

For the pure-component supercooled Lennard-Jones vapor, the free energy of forming a droplet with... more For the pure-component supercooled Lennard-Jones vapor, the free energy of forming a droplet with a given particle number and volume is calculated using density-functional theory. In contrast to what was noted in previous studies, the free energy surface beyond the pseudosaddle point no longer exhibits a valley but rather channels the nuclei toward a locus of instabilities, initiating an unstable growth phase. Similar to a previous study of bubble formation in superheated liquids [M. J. Uline and D. S. Corti, Phys. Rev. Lett. 99, 076102 (2007)], a new picture of homogeneous droplet nucleation and growth emerges.

The Journal of Chemical Physics, 2008

We consider various ensemble averages within the molecular dynamics (MD) ensemble, corresponding ... more We consider various ensemble averages within the molecular dynamics (MD) ensemble, corresponding to those states sampled during a MD simulation in which the application of periodic boundary conditions imposes a constraint on the momentum of the center of mass. As noted by Shirts et al. [J. Chem. Phys. 125, 164102 (2006)] for an isolated system, we find that the principle of equipartition is not satisfied within such simulations, i.e., the total kinetic energy of the system is not shared equally among all the translational degrees of freedom. Nevertheless, we derive two different versions of Tolman's generalized equipartition theorem, one appropriate for the canonical ensemble and the other relevant to the microcanonical ensemble. In both cases, the breakdown of the principle of equipartition immediately follows from Tolman's result. The translational degrees of freedom are, however, still equivalent, being coupled to the same bulk property in an identical manner. We also show that the temperature of an isolated system is not directly proportional to the average of the total kinetic energy (in contrast to the direct proportionality that arises between the temperature of the external bath and the kinetic energy within the canonical ensemble). Consequently, the system temperature does not appear within Tolman's generalized equipartition theorem for the microcanonical ensemble (unlike the immediate appearance of the temperature of the external bath within the canonical ensemble). Both of these results serve to highlight the flaws in the argument put forth by Hertz [Ann. Phys. 33, 225 (1910); 33, 537 (1910)] for defining the entropy of an isolated system via the integral of the phase space volume. Only the Boltzmann-Planck entropy definition, which connects entropy to the integral of the phase space density, leads to the correct description of the properties of a finite, isolated system. We demonstrate that the use of the integral of the phase space volume leads to unphysical results, indicating that the property of adiabatic invariance has little to do with the behavior of small systems.

The Journal of Chemical Physics, 2008

Based on the approach of Gruhn and Monson [Phys. Rev. E 63, 061106 (2001)], we present a new meth... more Based on the approach of Gruhn and Monson [Phys. Rev. E 63, 061106 (2001)], we present a new method for deriving the collisions dynamics for particles that interact via discontinuous potentials. By invoking the conservation of the extended Hamiltonian, we generate molecular dynamics (MD) algorithms for simulating the hard-sphere and square-well fluids within the isothermal-isobaric (NpT) ensemble. Consistent with the recent rigorous reformulation of the NpT ensemble partition function, the equations of motion impose a constant external pressure via the introduction of a shell particle of known mass [M. J. Uline and D. S. Corti, J. Chem. Phys. 123, 164101 (2005); 123, 164102 (2005)], which serves to define uniquely the volume of the system. The particles are also connected to a temperature reservoir through the use of a chain of Nose-Hoover thermostats, the properties of which are not affected by a hard-sphere or square-well collision. By using the Liouville operator formalism and the Trotter expansion theorem to integrate the equations of motion, the update of the thermostat variables can be decoupled from the update of the positions of the particles and the momentum changes upon a collision. Hence, once the appropriate collision dynamics for the isobaric-isenthalpic (NpH) equations of motion is known, the adaptation of the algorithm to the NpT ensemble is straightforward. Results of MD simulations for the pure component square-well fluid are presented and serve to validate our algorithm. Finally, since the mass of the shell particle is known, the system itself, and not a piston of arbitrary mass, controls the time scales for internal pressure and volume fluctuations. We therefore consider the influence of the shell particle algorithm on the dynamics of the square-well fluid.

Journal of Chemical Education, 2006

ABSTRACT

Faraday Discussions, 2013

Using microscopic molecular theory, we determine the bending and saddle-splay constants of three-... more Using microscopic molecular theory, we determine the bending and saddle-splay constants of three-component lipid bilayers. The membrane contains cholesterol, dipalmitoyl-phosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC) and the predictions of the theory have been shown to qualitatively reproduce phase diagrams of giant unilamellar vesicles (GUVs) of the same three components. The bending and saddle-splay constants were calculated for the gel, liquid-ordered (lo) and liquid-disordered (ld) phases. By proper expansion of the free energy, the molecular theory enables us to determine the effects of the mode of membrane bending deformation on the value of the elastic constants for different phases. In particular, we refer to the ability of the molecules to arrange the composition between the two monolayers upon deformation. The bending and saddle-splay constants obtained from the free energy expansion can be expressed in terms of moments of the local lateral pressures and their derivatives, all evaluated for a symmetric planar bilayer. The effect of blocked vs. free exchange of lipids across the two monolayers on the values of the bending constant is as high as 50 k(B)Tin the ld phase to as high as 200 k(B)T in the lo phase. These results show that one must strongly consider the mode of deformation in determining the mechanical properties of lipid bilayers. We discuss how the different contributions to the lateral pressures affect the values of the elastic constants, including the effects of the cholesterol concentration and temperature on the membrane elastic constants. We also calculate the equilibrium binding concentrations of lipid tail anchors as a function of membrane curvature by explicitly determining the chemical potential difference of species across a curved bilayer. Our results are in excellent agreement with recent experimental results.

Biophysical Journal, 2010

Using a combination of all-atom and coarse-grained molecular dynamics simulations to interpret a ... more Using a combination of all-atom and coarse-grained molecular dynamics simulations to interpret a range of x-ray scattering experiments, we aim to understand the role of membrane deformation in the action of the Parkinson's Disease protein, a-Synuclein. Our simulation results have led to the hypothesis that aS flattens curved membranes by screening the repulsive interactions between negatively charged, acidic headgroups, thereby reducing the effective area per headgroup and relieving the inherent positive curvature of the lipids on the outer leaflet of synaptic vesicles. We hope to address the question of whether aS influences a membrane's mechanical properties as a route to evaluating this hypothesis. Additionally, we aim to understand the role of aS in recruiting sub-domains of positively charged lipids. A second, smaller peptide (the CRAC motif from gp41) is also studied in an effort to build the computational tools necessary for matching the x-ray data that is used for calculating a membrane's material properties.

Biophysical Journal, 2010

X-ray scattering is a promising tool with which to characterize systems of solidsupported membran... more X-ray scattering is a promising tool with which to characterize systems of solidsupported membranes. There are many different scattering techniques used in the characterization, but all suffer from a necessarily low electron density contrast between the membrane and the water medium in which it must exist. Labeling membranes with a high-contrast scatterer such as gold is a promising avenue to solve this problem. In this work, silicon-supported membranes of 1,2dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were prepared by both standard Langmuir-Blodgett deposition and fusion of vesicles onto the substrate surface. Membranes are characterized using specular x-ray reflectometry, and modeled to fit physical systems. One percent by count 1,2-dipalmitoyl-sn-glycero-phosphoethanolamine (DPPE) with a gold tag attached was then added to both systems. Gold labeled membranes were then characterized and modeled. The effect of gold labeling is shown to characteristically change the membrane density profile in addition to enhancing density contrast between the membrane and the water medium. We created two-dimensional (2D) assemblies of tobacco mosaic viruses (TMVs) and characterized their structures using Atomic Force Microscopy (AFM) and X-ray scattering. The TMVs were adsorbed on an oppositely charged, fluid lipid monolayer supported by a solid substrate and submerged in a buffer solution. The lipid monolayer confined the viral particles within a plane, while providing them with lateral mobility so that overall the TMV assembly behaved like a 2D liquid. The inter-particle interaction is controlled by the chemical condition in the buffer. The degree of structural orders observed varied, depending on both the inter-particle interaction and the lateral mobility of the particles. Quantitative analysis of the X-ray scattering data provides information on the nature of the interaction between TMVs as well as possible membrane deformation due to the contact with TMVs. This study provides the proof-of-concept that X-ray scattering may be used to study the structure of membrane associated proteins in substrate-supported single bilayer under near-native conditions.

Biophysical Journal, 2011

Pulmonary surfactant (PS) is a surface active lipoproteic material produced by type II cells at t... more Pulmonary surfactant (PS) is a surface active lipoproteic material produced by type II cells at the alveoli. This material forms a unique air-liquid interface lining the alveolar surface that reduces surface tension close to 0mN/m, maintaining lung volumes and alveolar homeostasis at the end of expiration. The particular lipid composition of PS suggests that mono-and bilayer-based structures should exhibit lateral phase segregation at physiological temperatures. This work on Native Pulmonary Surfactant Membranes (NPSM), directly isolated from broncho-alveolar lavages of wild-type mice show that a detailed lipid compositional study is crucial to understand the structure and biophysical function of these complex mixtures. Using different microscopy techniques, we have managed to analyze, in detail at the micro-and nano-scale, qualitative and quantitatively the whole native interfacial film responsible for breathing in mice. First, it was performed a study of the lipid phase segregation pattern on free-standing spherical and in planar solidsupported bilayers. Then, the phase behavior was investigated in planar solid-supported and in in-situ air-liquid monolayers. We found close correspondence in shape, size, height, area coverage and lipid phase of the domains between bilayers and monolayers. Contrary to what has been published until now. Particularly with monolayers, the quantification of the order among the different coexisting lipid phases indicates that the segregated rounded domains within a percolated larger area are more fluid. The phase segregation pattern remains until physiological relevant respiratory surface pressures, where we found non-homogeneous nanostructure serving as a platform for a highly corrugated-like collapsed structures, that grow size-and heightwise, arising from the more fluid phases. This last finding opens a new way to explore the pulmonary surfactant interfacial films, closer to materials science, which could help to understand such a basic and important topic; the respiration in mammals.

Biophysical Journal, 2010

We calculate partition coefficients of various chain anchors in liquid-ordered and liquid-disorde... more 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.

Langmuir, 2011

Charge regulation in polyacid monolayers attached at one end to a planar surface is studied theor... more Charge regulation in polyacid monolayers attached at one end to a planar surface is studied theoretically. The polyacid layers are designed to mimic single-stranded DNA monolayers. The effects of the local pH and salt concentration on the protonation states of the polyacid layer are studied using a molecular mean-field theory that includes a microscopic description of the conformations of the polyacid molecule along with electrostatic interactions, acid-base equilibrium, and excluded volume interactions. We predict that, in the case of a monovalent salt, NaCl, the amount of proton binding increases dramatically for high surface coverage of polyacid and low bulk salt concentration. When the polyelectrolyte is almost completely charge neutralized by bound protons, there is an expulsion of sodium from the layer. We show that the degree of protonation can go all the way from 0% to 100% when the bulk pH is kept fixed at 7 by changing the surface coverage of polyacid and the bulk salt concentration. The effects of increasing protonation and the expulsion of the cations from the monolayer are reduced when sodium ions are replaced by divalent magnesium ions. Our theoretical results concur with X-ray photoelectron spectroscopy studies of ssDNA monolayers on gold.