Publications by authors named "Kathleen D Cao"

9 Publications

  • Page 1 of 1

Tailoring Biomimetic Phosphorylcholine-Containing Block Copolymers as Membrane-Targeting Cellular Rescue Agents.

Biomacromolecules 2019 09 19;20(9):3385-3391. Epub 2019 Aug 19.

Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute , The University of Chicago , Chicago , Illinois 60637 , United States.

Some synthetic polymers can block cell death when applied following an injury that would otherwise kill the cell. This cellular rescue occurs through interactions of the polymers with cell membranes. However, general principles for designing synthetic polymers to ensure strong, but nondisruptive, cell membrane targeting are not fully elucidated. Here, we tailored biomimetic phosphorylcholine-containing block copolymers to interact with cell membranes and determined their efficacy in blocking neuronal death following oxygen-glucose deprivation. By adjusting the hydrophilicity and membrane affinity of poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC)-based triblock copolymers, the surface active regime in which the copolymers function effectively as membrane-targeting cellular rescue agents was determined. We identified nonintrusive interactions between the polymer and the cell membrane that alter the collective dynamics of the membrane by inducing rigidification without disrupting lipid packing or membrane thickness. In general, our results open new avenues for biological applications of polyMPC-based polymers and provide an approach to designing membrane-targeting agents to block cell death after injury.
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http://dx.doi.org/10.1021/acs.biomac.9b00621DOI Listing
September 2019

Enhanced Ordering in Monolayers Containing Glycosphingolipids: Impact of Carbohydrate Structure.

Biophys J 2018 03;114(5):1103-1115

Department of Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, Illinois. Electronic address:

The influence of carbohydrate structure on the ordering of glycosphingolipids (GSLs) and surrounding phospholipids was investigated in monolayers at the air-water interface. Binary mixtures composed of GSLs, chosen to span a range of carbohydrate complexity, and zwitterionic dipalmitoylphosphatidylcholine phospholipid, were studied. X-ray reflectivity was used to measure the out-of-plane structure of the monolayers and characterize the extension and conformation of the GSL carbohydrates. Using synchrotron grazing incidence x-ray diffraction, the in-plane packing of the lipid acyl chains and the area per molecule within ordered domains were characterized at different mole ratios of the two components. Our findings indicate that GSL-containing mixtures, regardless of the carbohydrate size, enhance the ordering of the surrounding lipids, resulting in a larger fraction of ordered phase of the monolayer and greater dimensions of the ordered domains. Reduction of the averaged area per molecule within the ordered domains was also observed but only in the cases where there was a size mismatch between the phospholipid headgroups and GSL components, suggesting that the condensation mechanism involves the relief of steric interactions between headgroups in mixtures.
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http://dx.doi.org/10.1016/j.bpj.2017.12.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883550PMC
March 2018

Quantitative analysis of total reflection X-ray fluorescence from finely layered structures using XeRay.

Rev Sci Instrum 2017 Mar;88(3):033112

James Franck Institute, The University of Chicago, Chicago, Illinois 60637, USA.

Total reflection x-ray fluorescence (TXRF) is a widely applicable experimental technique for studying chemical element distributions across finely layered structures at extremely high sensitivity. To promote and facilitate scientific discovery using TXRF, we developed a MATLAB-based software package with a graphical user interface, named XeRay, for quick, accurate, and intuitive data analysis. XeRay lets the user model any layered system, each layer with its independent chemical composition and thickness, and enables fine-tuned data fitting. The accuracy of XeRay has been tested in the analysis of TXRF data from both air/liquid interface and liquid/liquid interfacial studies and has been compared to literature results. In an air/liquid interface study, Ca sequestration was measured at a Langmuir monolayer of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphatidic acid (SOPA) on a buffer solution of 1 mM CaCl at pH 7.5. Data analysis with XeRay reveals that each 1 nm of interfacial area contains 2.38 ± 0.06 Ca ions, which corresponds to a 1:1 ratio between SOPA headgroups and Ca ions, consistent with several earlier reports. For the liquid/liquid interface study of Sr enrichment at the dodecane/surfactant/water interface, analysis using XeRay gives a surface enrichment of Sr at 68 Å per ion, consistent with the result published for the same dataset.
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http://dx.doi.org/10.1063/1.4978654DOI Listing
March 2017

Mechanical Stability of Polystyrene and Janus Particle Monolayers at the Air/Water Interface.

J Am Chem Soc 2015 Dec 1;137(49):15370-3. Epub 2015 Dec 1.

Department of Chemical Engineering, City College of City University of New York , New York, New York 10031, United States.

The compressional instability of particle-laden air/water interfaces is investigated with plain and surface-anisotropic (Janus) particles. We hypothesize that the amphiphilic nature of Janus particles leads to both anisotropic particle-particle and particle-interface interactions that can yield particle films with unique collapse mechanisms. Analysis of Langmuir isotherms and microstructural characterization of the homogeneous polystyrene particle films during compression reveal an interfacial buckling instability followed by folding, which is in good agreement with predictions from classical elasticity theory. In contrast, Janus particle films exhibit a different behavior during compression, where the collapse mode occurs through the subduction of the Janus particle film. Our results suggest that particle-laden films comprised of surface-anisotropic particles can be engineered to evolve new material properties.
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http://dx.doi.org/10.1021/jacs.5b10183DOI Listing
December 2015

Collapse of Particle-Laden Interfaces under Compression: Buckling vs Particle Expulsion.

Langmuir 2015 Jul 6;31(28):7764-75. Epub 2015 Jul 6.

†Department of Chemical Engineering, City College of City University of New York, New York, New York 10031, United States.

Colloidal particles can bind to fluid interfaces with a capillary energy that is thousands of times the thermal energy. This phenomenon offers an effective route to emulsion and foam stabilization where the stability is influenced by the phase behavior of the particle-laden interface under deformation. Despite the vast interest in particle-laden interfaces, the key factors that determine the collapse of such an interface under compression have remained relatively unexplored. In this study, we illustrate the significance of the particle surface wettability and presence of electrolyte in the subphase on interparticle interactions at the interface and the resulting collapse mode. Various collapse mechanisms including buckling, particle expulsion, and multilayer formation are reported and interpreted in terms of particle-particle and particle-interface interactions.
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http://dx.doi.org/10.1021/acs.langmuir.5b01652DOI Listing
July 2015

Influence of molecular coherence on surface viscosity.

Langmuir 2014 Jul 14;30(29):8829-38. Epub 2014 Jul 14.

Chemical Engineering and Materials Science, University of Minnesota , Minneapolis, Minnesota 55455, United States.

Adding small fractions of cholesterol decreases the interfacial viscosity of dipalmitoylphosphatidylcholine (DPPC) monolayers by an order of magnitude per wt %. Grazing incidence X-ray diffraction shows that cholesterol at these small fractions does not mix ideally with DPPC but rather induces nanophase separated structures of an ordered, primarily DPPC phase bordered by a line-active, disordered, mixed DPPC-cholesterol phase. We propose that the free area in the classic Cohen and Turnbull model of viscosity is inversely proportional to the number of molecules in the coherence area, or product of the two coherence lengths. Cholesterol significantly reduces the coherence area of the crystals as well as the interfacial viscosity. Using this free area collapses the surface viscosity data for all surface pressures and cholesterol fractions to a universal logarithmic relation. The extent of molecular coherence appears to be a fundamental factor in determining surface viscosity in ordered monolayers.
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http://dx.doi.org/10.1021/la501615gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334248PMC
July 2014

Molecular mechanism for differential recognition of membrane phosphatidylserine by the immune regulatory receptor Tim4.

Proc Natl Acad Sci U S A 2014 Apr 31;111(15):E1463-72. Epub 2014 Mar 31.

Program in Biophysical Sciences, Institute for Biophysical Dynamics, Department of Chemistry, and James Franck Institute, The University of Chicago, Chicago, IL 60637.

Recognition of phosphatidylserine (PS) lipids exposed on the extracellular leaflet of plasma membranes is implicated in both apoptotic cell removal and immune regulation. The PS receptor T cell immunoglobulin and mucin-domain-containing molecule 4 (Tim4) regulates T-cell immunity via phagocytosis of both apoptotic (high PS exposure) and nonapoptotic (intermediate PS exposure) activated T cells. The latter population must be removed at lower efficiency to sensitively control immune tolerance and memory cell population size, but the molecular basis for how Tim4 achieves this sensitivity is unknown. Using a combination of interfacial X-ray scattering, molecular dynamics simulations, and membrane binding assays, we demonstrate how Tim4 recognizes PS in the context of a lipid bilayer. Our data reveal that in addition to the known Ca(2+)-coordinated, single-PS binding pocket, Tim4 has four weaker sites of potential ionic interactions with PS lipids. This organization makes Tim4 sensitive to PS surface concentration in a manner capable of supporting differential recognition on the basis of PS exposure level. The structurally homologous, but functionally distinct, Tim1 and Tim3 are significantly less sensitive to PS surface density, likely reflecting the differences in immunological function between the Tim proteins. These results establish the potential for lipid membrane parameters, such as PS surface density, to play a critical role in facilitating selective recognition of PS-exposing cells. Furthermore, our multidisciplinary approach overcomes the difficulties associated with characterizing dynamic protein/membrane systems to reveal the molecular mechanisms underlying Tim4's recognition properties, and thereby provides an approach capable of providing atomic-level detail to uncover the nuances of protein/membrane interactions.
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http://dx.doi.org/10.1073/pnas.1320174111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992656PMC
April 2014

Glycerol-induced membrane stiffening: the role of viscous fluid adlayers.

Biophys J 2011 Jul;101(1):118-27

Department of Chemistry, University of Chicago, Chicago, Illinois, USA.

Lipid interfaces, ranging from cell membranes to thin surfactant layers that stabilize lung alveoli, are integral to living systems. Such interfaces are often subjected to mechanical forces, and because of their membrane-like geometry, they can easily deform by bending into localized folds. In this work, we explore the role of small molecules (i.e., glycerol) on the mechanical stability of model lung surfactant monolayers. We demonstrate that the presence of glycerol increases local monolayer bending stiffness by orders of magnitude. Our x-ray and neutron reflectivity measurements indicate that water is preferentially depleted, or glycerol is preferentially enriched, at the lipid headgroup/solvent interface, and that this glycerol-enriched layer extends O(10Å) beneath the monolayer with an adsorption free energy of -2.5 to -4.6 kJ/mol. The dramatic change in membrane bending stiffness in the presence of the sugar adlayer is understood in terms of two models: 1), lipid antiplasticization by glycerol; and 2), a continuum mechanical model of the viscous adlayer.
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http://dx.doi.org/10.1016/j.bpj.2011.05.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127174PMC
July 2011

Ordered nanoclusters in lipid-cholesterol membranes.

Phys Rev Lett 2009 Jul 8;103(2):028103. Epub 2009 Jul 8.

Department of Physics, Institute for Biophysical Dynamics, and The James Franck Institute, The University of Chicago, 929 E. 57th Street, Chicago, Illinois 60637, USA.

X-ray diffraction of sphingomyelin-dihydrocholesterol (SM-DChol) monolayers revealed short-ranged ( approximately 25 A) 2D ordering. These nanoclusters show two distinct regions: below the cusp point of the phase diagram (35 mol% DChol), a constant d spacing was observed; above the cusp, the d spacing increases linearly with DChol in accordance to Vegard's law for binary alloys. The components in this lipidic alloy are thus a 65ratio35 SM-DChol entity and excess DChol. Reflectivity data further support the emergence above the cusp of an uncomplexed DChol population with greater vertical mobility.
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http://dx.doi.org/10.1103/PhysRevLett.103.028103DOI Listing
July 2009