Hydrophobic Mismatch Research Articles

Altered lipid acyl chain length controls energy dissipation in light-harvesting complex II proteoliposomes by hydrophobic mismatch.

In plants, the major light-harvesting antenna complex (LHCII) is vital for both light harvesting and photoprotection in photosystem II. Previously, we proposed that the thylakoid membrane itself could switch LHCII into the photoprotective state, qE, via a process known as hydrophobic mismatch. The decrease in the membrane thickness that followed the formation of ΔpH was a key fact that prompted this idea. To test this, we made proteoliposomes from lipids with altered acyl chain length (ACL). Here, we show that ACL regulates the average chlorophyll fluorescence lifetime of LHCII. For liposomes made of lipids with an ACL of 18 carbons, the lifetime was ∼2ns, like that for the thylakoid membrane. Furthermore, LHCII appears to be quenched in proteoliposomes with an ACL both shorter and longer than 18 carbons. The proteoliposomes made of short ACL lipids display structural heterogeneity revealing two quenched conformations of LHCII, each having characteristic 77K fluorescence spectra. One conformation spectrally resembles isolated LHCII aggregates, whilst the other resembles LHCII immobilized in polyacrylamide gels. Overall, the decrease in the ACL appears to produce quenched conformations of LHCII, which renders plausible the idea that the trigger of qE is the hydrophobic mismatch.

Surfactant-Mediated Structural Modulations to Planar, Amphiphilic Multilamellar Stacks.

The hydrophobic effect, a ubiquitous process in biology, is a primary thermodynamic driver of amphiphilic self-assembly. It leads to the formation of unique morphologies including two highly important classes of lamellar and micellar mesophases. The interactions between these two types of structures and their involved components have garnered significant interest because of their importance in key biochemical technologies related to the isolation, purification, and reconstitution of membrane proteins. This work investigates the structural organization of mixtures of the lamellar-forming phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and two zwitterionic micelle-forming surfactants, being n-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (Zwittergent 3-12 or DDAPS) and 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (O-Lyso-PC), when assembled by water vapor hydration with X-ray diffraction measurements, brightfield optical microscopy, wide-field fluorescence microscopy, and atomic force microscopy. The results reveal that multilamellar mesophases of these mixtures can be assembled across a wide range of POPC to surfactant (POPC:surfactant) concentration ratios, including ratios far surpassing the classical detergent-saturation limit of POPC bilayers without significant morphological disruptions to the lamellar motif. The mixed mesophases generally decreased in lamellar spacing (D) and headgroup-to-headgroup distance (Dhh) with a higher concentration of the doped surfactant, but trends in water layer thickness (Dw) between each bilayer in the stack are highly variable. Further structural characteristics including mesophase topography, bilayer thickness, and lamellar rupture force were revealed by atomic force microscopy (AFM), exhibiting homogeneous multilamellar stacks with no significant physical differences with changes in the surfactant concentration within the mesophases. Taken together, the outcomes present the assembly of unanticipated and highly unique mixed mesophases with varied structural trends from the involved surfactant and lipidic components. Modulations in their structural properties can be attributed to the surfactant's chemical specificity in relation to POPC, such as the headgroup hydration and the hydrophobic chain tail mismatch. Taken together, our results illustrate how specific chemical complexities of surfactant-lipid interactions can alter the morphologies of mixed mesophases and thereby alter the kinetic pathways by which surfactants dissolve lipid mesophases in bulk aqueous solutions.

In Search of a Molecular View of Peptide-Lipid Interactions in Membranes.

Lipid bilayer membranes are often represented as a continuous nonpolar slab with a certain thickness bounded by two more polar interfaces. Phenomena such as peptide binding to the membrane surface, folding, insertion, translocation, and diffusion are typically interpreted on the basis of this view. In this Perspective, I argue that this membrane representation as a hydrophobic continuum solvent is not adequate to understand peptide-lipid interactions. Lipids are not small compared to membrane-active peptides: their sizes are similar. Therefore, peptide diffusion needs to be understood in terms of free volume, not classical continuum mechanics; peptide solubility or partitioning in membranes cannot be interpreted in terms of hydrophobic mismatch between membrane thickness and peptide length; peptide folding and translocation, often involving cationic peptides, can only be understood if realizing that lipids adapt to the presence of peptides and the membrane may undergo considerable lipid redistribution in the process. In all of those instances, the detailed molecular interactions between the peptide residues and the lipid components are essential to understand the mechanisms involved.

Hypo-Osmotic Stress and Pore-Forming Toxins Adjust the Lipid Order in Sheep Red Blood Cell Membranes.

Lipid ordering in cell membranes has been increasingly recognized as an important factor in establishing and regulating a large variety of biological functions. Multiple investigations into lipid organization focused on assessing ordering from temperature-induced phase transitions, which are often well outside the physiological range. However, particular stresses elicited by environmental factors, such as hypo-osmotic stress or protein insertion into membranes, with respect to changes in lipid status and ordering at constant temperature are insufficiently described. To fill these gaps in our knowledge, we exploited the well-established ability of environmentally sensitive membrane probes to detect intramembrane changes at the molecular level. Our steady state fluorescence spectroscopy experiments focused on assessing changes in optical responses of Laurdan and diphenylhexatriene upon exposure of red blood cells to hypo-osmotic stress and pore-forming toxins at room temperature. We verified our utilized experimental systems by a direct comparison of the results with prior reports on artificial membranes and cholesterol-depleted membranes undergoing temperature changes. The significant changes observed in the lipid order after exposure to hypo-osmotic stress or pore-forming toxins resembled phase transitions of lipids in membranes, which we explained by considering the short-range interactions between membrane components and the hydrophobic mismatch between membrane thickness and inserted proteins. Our results suggest that measurements of optical responses from the membrane probes constitute an appropriate method for assessing the status of lipids and phase transitions in target membranes exposed to mechanical stresses or upon the insertion of transmembrane proteins.

Phosphatidylinositol 4,5-Bisphosphate Sensing Lipid Raft via Inter-Leaflet Coupling Regulated by Acyl Chain Length of Sphingomyelin

Phosphatidylinositol 4,5-bisphosphate (PIP2) is an important molecule located at the inner leaflet of cell membrane, where it serves as anchoring sites for a cohort of membrane-associated molecules and as a broad-reaching signaling intermediate. The lipid raft is thought as the major platform recruiting proteins for signal transduction and also known to mediate PIP2 accumulation across the membrane. While the significance of this cross-membrane coupling is increasingly appreciated, it remains unclear whether and how PIP2 senses the dynamic change of the ordered lipid domains over the packed hydrophobic core of the bilayer. Herein, by means of molecular dynamic simulation, we reveal that inner PIP2 molecules can sense the outer lipid domain via inter-leaflet coupling, and the coupling manner is dictated by the acyl chain length of sphingomyelin (SM) partitioned to the lipid domain. Shorter SM promotes membrane domain registration, whereby PIP2 accumulates beneath the domain across the membrane. In contrast, the anti-registration is thermodynamically preferred if the lipid domain has longer SM due to the hydrophobic mismatch between the corresponding acyl chains in SM and PIP2. In this case, PIP2 is expelled by the domain with a higher diffusivity. These results provide molecular insights into the regulatory mechanism of correlation between the outer lipid domain and inner PIP2, both of which are critical components for cell signal transduction.

Allosteric modulation of integral protein activity by differential stress in asymmetric membranes.

The activity of integral membrane proteins is tightly coupled to the properties of the surrounding lipid matrix. In particular, transbilayer asymmetry, a hallmark of all plasma membranes, might be exploited to control membrane-protein activity. Here, we hypothesized that the membrane-embedded enzyme outer membrane phospholipase A (OmpLA) is susceptible to the lateral pressure differences that build up between such asymmetric membrane leaflets. Upon reconstituting OmpLA into synthetic, chemically well-defined phospholipid bilayers exhibiting different lateral pressure profiles, we indeed observed a substantial decrease in the enzyme's hydrolytic activity with increasing membrane asymmetry. No such effects were observed in symmetric mixtures of the same lipids. To quantitatively rationalize how the differential stress in asymmetric lipid bilayers inhibits OmpLA, we developed a simple allosteric model within the lateral pressure framework. Thus, we find that membrane asymmetry can serve as the dominant factor in controlling membrane-protein activity, even in the absence of specific, chemical cues or other physical membrane determinants such as hydrophobic mismatch.

How lipids modulate association of proteins in lipid membranes.

Membrane proteins mediate most specific functions of cellular membranes, including energy conversion, selective transport of ions and nutrients, cellular recognition, and signaling. It is well established that the functional activity of membrane proteins depends on various physical and chemical parameters, among which membrane lipid composition is one of the factors that has been widely explored. As membrane proteins perform their function, they often associate with each other. At the molecular level, these protein-membrane interactions can be fine-tuned by two crucial mechanical properties of the lipid membrane: i) the membrane thickness and ii) the lipid packing, a measure of how tightly lipid tails fit against each other. Accordingly, the current project aims to quantify to what extent hydrophobic mismatch (that is, the difference between the length of the protein and the thickness of the hydrophobic core of the membrane) and lipid packing contribute to the protein association using molecular dynamics simulations. Specifically, we aim to determine sequence-independent contributions to the thermodynamics of dimer stabilization, as well as the molecular basis of the hydrophobic mismatch. We expect to find a simple, additive relationship between hydrophobic mismatch, lipid packing, and the free energy of dimer formation. To capture sequence-independent trends in protein association, we propose a simplified representation of a transmembrane helix. Our model will allow controlling the extent of the hydrophobic mismatch simply by changing the length of the helix model and adjusting parameters such as particle diameter or surface roughness to mimic other biological peptides.

The mechanism of dwarf open reading frame (DWORF) activation of the sarcoplasmic reticulum calcium pump SERCA.

The sarcoplasmic reticulum calcium pump SERCA plays a critical role in the contraction-relaxation cycle of muscle. In cardiac muscle, SERCA is regulated by the inhibitory transmembrane peptide phospholamban. A new transmembrane peptide regulator, dwarf open reading frame (DWORF), has been reported to displace phospholamban from SERCA. We have shown that DWORF is a direct activator of SERCA, increasing its turnover rate in the absence of phospholamban (1). Measurement of in-cell calcium dynamics supports this observation and demonstrates that DWORF increases SERCA-dependent calcium reuptake, while phospholamban decreases SERCA-dependent calcium reuptake. These functional observations reveal opposing effects of DWORF activation and phospholamban inhibition of SERCA. To gain mechanistic insight into SERCA activation, fluorescence resonance energy transfer experiments revealed that DWORF has a higher affinity for SERCA in the presence of calcium, while phospholamban has a higher affinity for SERCA in the absence of calcium. Molecular modeling and molecular dynamics simulations provide a model for DWORF activation of SERCA, where DWORF modulates the membrane bilayer and stabilizes the conformations of SERCA that predominate during elevated cytosolic calcium. Mutagenesis and structure-function analysis of DWORF reveals three important features required for SERCA activation: Pro15 promotes a helix-linker-helix structure of DWORF; the N-terminal amphipathic helix of DWORF perturbs the membrane bilayer; and the short transmembrane helix of DWORF contributes to hydrophobic mismatch and positions the amphipathic helix at the surface of the membrane bilayer. Our current understanding of the mechanism of SERCA activation by DWORF will be presented.

Length matters: Functional flip of the short TatA transmembrane helix

The twin arginine translocase (Tat) exports folded proteins across bacterial membranes. The putative pore-forming or membrane-weakening component (TatAd in B. subtilis) is anchored to the lipid bilayer via an unusually short transmembrane α-helix (TMH), with less than 16 residues. Its tilt angle in different membranes was analyzed under hydrophobic mismatch conditions, using synchrotron radiation circular dichroism and solid-state NMR. Positive mismatch (introduced either by reconstitution in short-chain lipids or by extending the hydrophobic TMH length) increased the helix tilt of the TMH as expected. Negative mismatch (introduced either by reconstitution in long-chain lipids or by shortening the TMH), on the other hand, led to protein aggregation. These data suggest that the TMH of TatA is just about long enough for stable membrane insertion. At the same time, its short length is a crucial factor for successful translocation, as demonstrated here in native membrane vesicles using an in vitro translocation assay. Furthermore, when reconstituted in model membranes with negative spontaneous curvature, the TMH was found to be aligned parallel to the membrane surface. This intrinsic ability of TatA to flip out of the membrane core thus seems to play a key role in its membrane-destabilizing effect during Tat-dependent translocation.

Interactions of Surfactants with the Bacterial Cell Wall and Inner Membrane: Revealing the Link between Aggregation and Antimicrobial Activity.

Surfactants with their intrinsic ability to solubilize lipid membranes are widely used as antibacterial agents, and their interactions with the bacterial cell envelope are complicated by their differential aggregation tendencies. We present a combined experimental and molecular dynamics investigation to unravel the molecular basis for the superior antimicrobial activity and faster kill kinetics of shorter-chain fatty acid surfactant, laurate, when compared with the longer-chain surfactants studied in contact time assays with live Escherichia coli (E. coli). From all-atom molecular dynamics simulations, translocation events across peptidoglycan were the highest for laurate followed by sodium dodecyl sulfate, myristate, palmitate, oleate, and stearate. The translocation kinetics were positively correlated with the critical micellar concentration, which determined the free monomer surfactant concentration available for translocation across peptidoglycan. Interestingly, aggregates showed a lower propensity to translocate across the peptidoglycan layer and longer translocation times were observed for oleate, thereby revealing an intrinsic sieving property of the bacterial cell wall. Molecular dynamics simulations with surfactant-incorporated bacterial inner membranes revealed the greatest hydrophobic mismatch and membrane thinning in the presence of laurate when compared with the other surfactants. The enhanced antimicrobial efficacy of laurate over oleate was further verified by experiments with giant unilamellar vesicles, and electroporation molecular dynamics simulations revealed greater inner membrane poration tendency in the presence of laurate when compared with the longer-chain surfactants. Our study provides molecular insights into surfactant translocation across peptidoglycan and chain length-induced structural disruption of the inner membrane, which correlate with contact time kill efficacies observed as a function of chain length with E. coli. The insights gained from our study uncover unexplored barrier properties of the bacterial cell envelope to rationalize the development of antimicrobial formulations and therapeutics.

Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration

To infect, enveloped viruses employ spike protein, spearheaded by its amphipathic fusion peptide (FP), that upon activation extends out from the viral surface to embed into the target cellular membrane. Here we report that synthesized influenza virus FPs are membrane active, generating pores in giant unilamellar vesicles (GUV), and thus potentially explain both influenza virus’ hemolytic activity and the liposome poration seen in cryo-electron tomography. Experimentally, FPs are heterogeneously distributed on the GUV at the time of poration. Consistent with this heterogeneous distribution, molecular dynamics (MD) simulations of asymmetric bilayers with different numbers of FPs in one leaflet show FP aggregation. At the center of FP aggregates, a profound change in the membrane structure results in thinning, higher water permeability, and curvature. Ultimately, a hybrid bilayer nanodomain forms with one lipidic leaflet and one peptidic leaflet. Membrane elastic theory predicts a reduced barrier to water pore formation when even a dimer of FPs thins the membrane as above, and the FPs of that dimer tilt, to continue the leaflet bending initiated by the hydrophobic mismatch between the FP dimer and the surrounding lipid.

Membrane-mediated protein interactions drive membrane protein organization

The plasma membrane’s main constituents, i.e., phospholipids and membrane proteins, are known to be organized in lipid-protein functional domains and supercomplexes. No active membrane-intrinsic process is known to establish membrane organization. Thus, the interplay of thermal fluctuations and the biophysical determinants of membrane-mediated protein interactions must be considered to understand membrane protein organization. Here, we used high-speed atomic force microscopy and kinetic and membrane elastic theory to investigate the behavior of a model membrane protein in oligomerization and assembly in controlled lipid environments. We find that membrane hydrophobic mismatch modulates oligomerization and assembly energetics, and 2D organization. Our experimental and theoretical frameworks reveal how membrane organization can emerge from Brownian diffusion and a minimal set of physical properties of the membrane constituents.

Hydrophobic mismatch and sequence specificity compete when transmembrane helix-helix interactions are measured with the TOXCAT assay.

Genetic assays capable of measuring the propensity of transmembrane helices to oligomerize within the cytoplasmic membrane of the bacterium E. coli are frequently used when sequence-specificity in transmembrane helix-helix interactions is investigated. In the present study, dimerization of the well-investigated wild-type and G83I-mutated transmembrane helix of the human glycophorin A protein was studied. Gradual prolongation of the transmembrane helix at the C-terminus with Leu residues lead to pronounced changes in the dimerization propensity when measured with the TOXCAT assay. Thus, besides sequence specificity, hydrophobic mismatch between the hydrophobic core of a studied transmembrane helix and the E. coli membrane can impact the oligomerization propensity of a transmembrane helix. This suggests that the results of genetic assays aiming at determining interactions of heterologous transmembrane helices within the E. coli membrane do not necessarily solely reflect sequence specificity in transmembrane helix-helix interactions, but might be additionally modulated by topological and structural effects caused by hydrophobic mismatch.

Rhomboid-catalyzed intramembrane proteolysis requires hydrophobic matching with the surrounding lipid bilayer.

Membrane thinning by rhomboid proteins has been proposed to reduce hydrophobic mismatch, providing a unique environment for important functions ranging from intramembrane proteolysis to retrotranslocation in protein degradation. We show by in vitro reconstitution and solid-state nuclear magnetic resonance that the lipid environment of the Escherichia coli rhomboid protease GlpG influences its activity with an optimal hydrophobic membrane thickness between 24 and 26 Å. While phosphatidylcholine membranes are only negligibly altered by GlpG, in an E. coli–relevant lipid mix of phosphatidylethanolamine and phosphatidylglycerol, a thinning by 1.1 Å per leaflet is observed. Protease activity is strongly correlated with membrane thickness and shows no lipid headgroup specificity. We infer from these results that, by adjusting the thickness of specific membrane domains, membrane proteins shape the bilayer for their specific needs.

TatA and TatB generate a hydrophobic mismatch important for the function and assembly of the Tat translocon in Escherichia coli

The twin-arginine translocation (Tat) system serves to translocate folded proteins across energy-transducing membranes in bacteria, archaea, plastids, and some mitochondria. In Escherichia coli, TatA, TatB, and TatC constitute functional translocons. TatA and TatB both possess an N-terminal transmembrane helix (TMH) followed by an amphipathic helix. The TMHs of TatA and TatB generate a hydrophobic mismatch with the membrane, as the helices comprise only 12 consecutive hydrophobic residues; however, the purpose of this mismatch is unclear. Here, we shortened or extended this stretch of hydrophobic residues in either TatA, TatB, or both and analyzed effects on translocon function and assembly. We found the WT length helices functioned best, but some variation was clearly tolerated. Defects in function were exacerbated by simultaneous mutations in TatA and TatB, indicating partial compensation of mutations in each by the other. Furthermore, length variation in TatB destabilized TatBC-containing complexes, revealing that the 12-residue-length is important but not essential for this interaction and translocon assembly. To also address potential effects of helix length on TatA interactions, we characterized these interactions by molecular dynamics simulations, after having characterized the TatA assemblies by metal-tagging transmission electron microscopy. In these simulations, we found that interacting short TMHs of larger TatA assemblies were thinning the membrane and—together with laterally-aligned tilted amphipathic helices—generated a deep V-shaped membrane groove. We propose the 12 consecutive hydrophobic residues may thus serve to destabilize the membrane during Tat transport, and their conservation could represent a delicate compromise between functionality and minimization of proton leakage.

Studying KcsA Channel Clustering Using Single Channel Voltage-Clamp Fluorescence Imaging.

Oligomerization and complex formation play a key role for many membrane proteins and has been described to influence ion channel function in both neurons and the heart. In this study, we observed clustering of single KcsA channels in planar lipid bilayer using single molecule fluorescence, while simultaneously measuring single channel currents. Clustering coincided with cooperative opening of KcsA. We demonstrate that clustering was not caused by direct protein-protein interactions or hydrophobic mismatch with the lipid environment, as suggested earlier, but was mediated via microdomains induced by the channel in the lipid matrix. We found that single channel activity of KcsA requires conically-shaped lipids in the lamellar liquid-crystalline (Lα) phase, and the need for a negative spontaneous curvature seem to lead to the deformations in the membrane that cause the clustering. The method introduced here will be applicable to follow oligomerization of a wide range of membrane proteins.

Mechanochemical coupling of lipid organization and protein function through membrane thickness deformations

Cell membranes are composed of a great variety of protein and lipid species with distinct unperturbed hydrophobic thicknesses. To achieve hydrophobic matching, the lipid bilayer tends to deform around membrane proteins so as to match the protein hydrophobic thickness at bilayer-protein interfaces. Such protein-induced distortions of the lipid bilayer hydrophobic thickness incur a substantial energy cost that depends critically on the bilayer-protein hydrophobic mismatch, while distinct conformational states of membrane proteins often show distinct hydrophobic thicknesses. As a result, hydrophobic interactions between membrane proteins and lipids can yield a rich interplay of lipid-protein organization and transitions in protein conformational state. We combine here the membrane elasticity theory of protein-induced lipid bilayer thickness deformations with the Landau-Ginzburg theory of lipid domain formation to systematically explore the coupling between local lipid organization, lipid and protein hydrophobic thickness, and protein-induced lipid bilayer thickness deformations in membranes with heterogeneous lipid composition. We allow for a purely mechanical coupling of lipid and protein composition through the energetics of protein-induced lipid bilayer thickness deformations as well as a chemical coupling driven by preferential interactions between particular lipid and protein species. We find that the resulting lipid-protein organization can endow membrane proteins with diverse and controlled mechanical environments that, via protein-induced lipid bilayer thickness deformations, can strongly influence protein function. The theoretical approach employed here provides a general framework for the quantitative prediction of how membrane thickness deformations influence the joint organization and function of lipids and proteins in cell membranes.

An internal docking site stabilizes substrate binding to γ-secretase: Analysis by molecular dynamics simulations

Amyloid precursor protein (APP) is cleaved and processed sequentially by γ-secretase yielding amyloid β (Aβ) peptides of different lengths. Longer Aβ peptides are associated with the formation of neurotoxic plaques related to Alzheimer’s disease. Based on the APP substrate-bound structure of γ-secretase, we investigated the enzyme-substrate interaction using molecular dynamics simulations and generated model structures that represent the sequentially cleaved intermediates during the processing reaction. The simulations indicated an internal docking site providing strong enzyme-substrate packing interaction. In the enzyme-substrate complex, it is located close to the region where the helical conformation of the substrate is interrupted and continues toward the active site in an extended conformation. The internal docking site consists of two non-polar pockets that are preferentially filled by large hydrophobic or aromatic substrate side chains to stabilize binding. Placement of smaller residues such as glycine can trigger a shift in the cleavage pattern during the simulations or results in destabilization of substrate binding. The reduced packing by smaller residues also influences the hydration of the active site and the formation of a catalytically active state. The simulations on processed substrate intermediates and a substrate G33I mutation offer an explanation of the experimentally observed relative increase of short Aβ fragment production for this mutation. In addition, studies on a substrate K28A mutation indicate that the internal docking site opposes the tendency of substrate dissociation due to a hydrophobic mismatch at the membrane boundary caused by K28 during processing and substrate movement toward the enzyme active site. The proposed internal docking site could also be useful for the specific design of new γ-secretase modulators.

Hydrophobic mismatch is a key factor in protein transport across lipid bilayer membranes via the Tat pathway

The twin-arginine translocation (Tat) pathway transports folded proteins across membranes in bacteria, thylakoids, plant mitochondria, and archaea. In most species, the active Tat machinery consists of three independent subunits: TatA, TatB, and TatC. TatA and TatB possess short transmembrane alpha helices (TMHs), both of which are only 15 residues long in Escherichia coli. Such short TMHs cause a hydrophobic mismatch between Tat subunits and the membrane bilayer, although the functional significance of this mismatch is unclear. Here, we sought to address the functional importance of the hydrophobic mismatch in the Tat transport mechanism in E. coli. We conducted three different assays to evaluate the effect of TMH length mutants on Tat activity and observed that the TMHs of TatA and TatB appear to be evolutionarily tuned to 15 amino acids, with activity dropping off following any modification of this length. Surprisingly, TatA and TatB with as few as 11 residues in their TMHs can still insert into the membrane bilayer, albeit with a decline in membrane integrity. These findings support a model of Tat transport utilizing localized toroidal pores that form when the membrane bilayer is thinned to a critical threshold. In this context, we conclude that the 15-residue length of the TatA and TatB TMHs can be seen as a compromise between the need for some hydrophobic mismatch to allow the membrane to reversibly reach the threshold thinness required for toroidal pore formation and the permanently destabilizing effect of placing even shorter helices into these energy-transducing membranes.

Effects of Oil Phase on the Inversion of Pickering Emulsions Stabilized by Palmitic Acid Decorated Silica Nanoparticles

Pickering emulsions stabilized by the interaction of palmitic acid (PA) and silica nanoparticles (SiNPs) at the water/oil interface have been studied using different alkane oil phases. The interaction of palmitic acid and SiNPs has a strong synergistic character in relation to the emulsion stabilization, leading to an enhanced emulsion stability in relation to that stabilized only by the fatty acid. This results from the formation of fatty acid-nanoparticle complexes driven by hydrogen bond interactions, which favor particle attachment at the fluid interface, creating a rigid armor that minimizes droplet coalescence. The comparison of emulsions obtained using different alkanes as the oil phase has shown that the hydrophobic mismatch between the length of the alkane chain and the C16 hydrophobic chain of PA determines the nature of the emulsions, with the solubility of the fatty acid in the oil phase being a very important driving force governing the appearance of phase inversion.