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Cyclodextrin molecules are increasingly being used in biological research and as therapeutic agents to alter membrane cholesterol content, yet there is much to learn about their interactions with cell membranes. We present a biomembrane-based organic electronic platform capable of detecting interactions of cell membrane constituents with methyl-β-cyclodextrin (MβCD). This approach enables label-free sensing and quantification of changes in membrane integrity resulting from such interactions. In this work, we employ cholesterol-containing supported lipid bilayers (SLBs) formed on conducting polymer-coated electrodes to investigate how MβCD impacts membrane resistance. By examining the outcomes of MβCD interactions with SLBs of varying cholesterol content, we demonstrate that changes in membrane permeability or resistance can be used as a functional measure for predicting cyclodextrin-mediated cholesterol extraction from cellular membranes. Furthermore, we use the SLB platforms to electronically monitor cholesterol delivery to membranes following exposure to MβCD pre-loaded with cholesterol, observing that cholesterol enrichment is commensurate with an increase in resistance. This biomembrane-based bioelectronic sensing system offers a tool to quantify the modulation of membrane cholesterol content using membrane resistance and provides information regarding MβCD-mediated changes in membrane integrity. Given the importance of membrane integrity for barrier function in cells, such knowledge is essential for our fundamental understanding of MβCD as a membrane cholesterol modulator and therapeutic delivery vehicle.

Transmembrane proteins (TMPs) regulate processes occurring at the cell surface and are essential gatekeepers of information flow across the membrane. TMPs are difficult to study, given the complex environment of the membrane and its influence on protein conformation, mobility, biomolecule interaction, and activity. For the first time, we create mammalian biomembranes supported on a transparent, electrically conducting polymer surface, which enables dual electrical and optical monitoring of TMP function in its native membrane environment. Mammalian plasma membrane vesicles containing ATP-gated P2X2 ion channels self-assemble on a biocompatible polymer cushion that transduces the changes in ion flux during ATP exposure. This platform maintains the complexity of the native plasma membrane, the fluidity of its constituents, and protein orientation critical to ion channel function. We demonstrate the dual-modality readout using microscopy to characterize protein mobility by single-particle tracking and sensing of ATP gating of P2X2 using electrical impedance spectroscopy. This measurement of TMP activity important for pain sensing, neurological activity, and sensory activity raises new possibilities for drug screening and biosensing applications.

We investigated the physicochemical and transport phenomena governing the self-assembly of colloidal nanoparticles at the interface of two immiscible fluids. By combining in situ grazing-incidence small-angle X-ray scattering (GISAXS) with a temporal resolution of 200 ms and electron microscopy measurements, we gained new insights into the coupled effects of solvent spreading, nanoparticle assembly, and recession of the vapor-liquid interface on the morphology of the self-assembled thin films. We focus on oleate-passivated PbSe nanoparticles dispersed across an ethylene glycol subphase as a model system and demonstrate how solvent parameters such as surface tension, nanoparticle solubility, aromaticity, and polarity influence the mesoscale morphology of the nanoparticle superlattice. We discovered that a nanoparticle precursor monolayer film spreads in front of the bulk solution and influences the fluid spreading across the subphase. Improved understanding of the impact of kinetic phenomena (i.e., solvent spreading and evaporation) on the superlattice morphology is important to describe the formation mechanism and ultimately enable the assembly of high-quality superlattices with long-range order.

Reconstituted supported lipid bilayers (SLB) are widely used as in vitro cell-surface models because they are compatible with a variety of surface-based analytical techniques. However, one of the challenges of using SLBs as a model of the cell surface is the limited complexity in membrane composition, including the incorporation of transmembrane proteins and lipid diversity that may impact the activity of those proteins. Additionally, it is challenging to preserve the transmembrane protein native orientation, function, and mobility in SLBs. Here, we leverage the interaction between cell plasma membrane vesicles and polyelectrolyte brushes to create planar bilayers from cell plasma membrane vesicles that have budded from the cell surface. This approach promotes the direct incorporation of membrane proteins and other species into the planar bilayer without using detergent or reconstitution and preserves membrane constituents. Furthermore, the structure of the polyelectrolyte brush serves as a cushion between the planar bilayer and rigid supporting surface, limiting the interaction of the cytosolic domains of membrane proteins with this surface. Single particle tracking was used to analyze the motion of GPI-linked yellow fluorescent proteins (GPI-YFP) and neon-green fused transmembrane P2X2 receptors (P2X2-neon) and shows that this platform retains over 75% mobility of multipass transmembrane proteins in its native membrane environment. An enzyme accessibility assay confirmed that the protein orientation is preserved and results in the extracellular domain facing toward the bulk phase and the cytosolic side facing the support. Because the platform presented here retains the complexity of the cell plasma membrane and preserves protein orientation and mobility, it is a better representative mimic of native cell surfaces, which may find many applications in biological assays aimed at understanding cell membrane phenomena.

We expose the predominant diffusional pathways for In and As in InAs, as well as dopant Si atoms in InAs, using Nudged Elastic Band calculations in conjunction with accurate Density Functional Theory calculations of the energy of defective systems. Our results show that As is a very fast diffuser compared to In and Si for both vacancy-assisted and interstitially mediated mechanisms. Larger indium atoms, on the other hand, are very slow diffusers and strongly prefer to remain on the In sublattice. Silicon also prefers to stay in substitutional sites in the In sublattice, in agreement with the fact that Si is used to create n-doped InAs. We find that the mechanism by which Si diffuses within the InAs lattice is very unlikely to proceed via vacancy-assisted jumps, since these routes encounter energy barriers above 2 eV. In contrast, silicon can readily make interstitial jumps since they occur with energy barriers as small as 0.23 eV. This suggests that an interstitial diffusion mechanism is strongly preferred for Si diffusion in InAs which challenges the common presumption made for another similar III-V compound, namely GaAs, that Si diffusion takes place via a vacancy-assisted mechanism.

The supported lipid bilayer has been portrayed as a useful model of the cell membrane compatible with many biophysical tools and techniques that demonstrate its appeal in learning about the basic features of the plasma membrane. However, some of its potential has yet to be realized, particularly in the area of bilayer patterning and phase/composition heterogeneity. In this work, we generate contiguous bilayer patterns as a model system that captures the general features of membrane domains and lipid rafts. Micropatterned polymer templates of two types are investigated for generating patterned bilayer formation: polymer blotting and polymer lift-off stenciling. While these approaches have been used previously to create bilayer arrays by corralling bilayers patches with various types of boundaries impenetrable to bilayer diffusion, unique to the methods presented here, there are no physical barriers to diffusion. In this work, interfaces between contiguous lipid phases define the pattern shapes, with continuity between them allowing transfer of membrane-bound biomolecules between the phases. We examine effectors of membrane domain stability including temperature and cholesterol content to investigate domain dynamics. Contiguous patterning of supported bilayers as a model of lipid rafts expands the application of the SLB to an area with current appeal and brings with it a useful toolset for characterization and analysis. These combined tools should be helpful to researchers investigating lipid raft dynamics and function and biomolecule partitioning studies. Additionally, this patterning technique may be useful for applications such as bioseparations that exploit differences in lipid phase partitioning or creation of membranes that bind species like viruses preferentially at lipid phase boundaries, to name a few.

Phase stability of polymer nanocomposites (PNCs) composed of polymer-grafted SiO 2 nanoparticles (NPs) blended with high-molar-mass host polymer chains is investigated. We focus on blends in which the particle-grafted polymer, polyethylene glycol (PEG), and the host-atactic poly(methylmethacrylate) (PMMA) or PMMA/oligo-PEG blends-exhibit favorable enthalpic interactions. Small-angle X-ray scattering measurements are used to evaluate the phase stability of the blends and to report on the structure of the materials at intermediate and long length scales. By exploring SiO 2 -PEG/PMMA and SiO 2 -PEG/PMMA-PEG systems covering a wide range of molecular weights (M w ) of PMMA (1.1 kDa ≤ M w,PMMA ≤ 1.1 × 10 3 kDa) and tethered PEG (0.5 kDa ≤ M w , PEG ≤ 2 kDa), we are able to develop a comprehensive stability map for PNCs based on hairy NPs. At low M w,PEG , the phase behavior is dominated by entropic effects and the negative Flory-Huggins χ parameter between PEG and PMMA plays no role in phase stability. For higher M w,PEO and intermediate M w,PMMA , a crossover from entropy- to enthalpy-dominated behavior is observed, which leads to the phase stability in PNCs well beyond the conventional limits reported for SiO 2 -PEG/PEG mixtures. This enhanced mixing ceases above a critical M w,PMMA , where it is found that PMMA chains wet a sufficiently large number of SiO 2 -PEG particles to bridge and thereby destabilize the composites.