Emma Sparr - Academia.edu (original) (raw)

Papers by Emma Sparr

Biochimica Et Biophysica Acta - Proteins And Proteomics, May 1, 2019

Lipid-protein interactions in amyloid formation Lipid membranes and amyloid fibrils are dynamic s... more Lipid-protein interactions in amyloid formation Lipid membranes and amyloid fibrils are dynamic self-assembled structures that co-exist in biology and have a clear influence on each other. The amyloid-forming protein may perturb the structure and integrity of the membrane (Fig. 1A), and the presence of the membrane may trigger the protein aggregation. Equally important, the coexistence of these dynamic systems of proteins and lipids, respectively, may lead to the formation of co-aggregates (Fig. 1B) that are lipid-rich or protein rich (Fig. 2). The main driving force for protein aggregation lies in the hydrophobic interactions, and amphiphilic molecules, such as membrane lipids, can interfere or even take part of such association process. Here, it is important to realise that the lipid membrane is a selfassembled dynamic structure rather than an intact and inert entity, and the amphiphilic lipids can rearrange into new assemblies together with other macromolecules when the conditions change. The co-assembly process may thus lead to that lipids from the membrane are taken up into the amyloid aggregates during their formation (Fig. 1B) [1-3]. Moreover, co-assembly in vivo occurs in an environment that contains many other substances, which potentially could take part in the process as physiologically relevant factors that

Journal of Colloid and Interface Science, Mar 1, 2023

Frontiers in Molecular Biosciences, Oct 19, 2021

The dense accumulation of α-Synuclein fibrils in neurons is considered to be strongly associated ... more The dense accumulation of α-Synuclein fibrils in neurons is considered to be strongly associated with Parkinson's disease. These intracellular inclusions, called Lewy bodies, also contain significant amounts of lipids. To better understand such accumulations, it should be important to study α-Synuclein fibril formation under conditions where the fibrils lump together, mimicking what is observed in Lewy bodies. In the present study, we have therefore investigated the overall structural arrangements of α-synuclein fibrils, formed under mildly acidic conditions, pH 5.5, in pure buffer or in the presence of various model membrane systems, by means of small-angle neutron scattering (SANS). At this pH, α-synuclein fibrils are colloidally unstable and aggregate further into dense clusters. SANS intensities show a power law dependence on the scattering vector, q, indicating that the clusters can be described as mass fractal aggregates. The experimentally observed fractal dimension was d 2.6 ± 0.3. We further show that this fractal dimension can be reproduced using a simple model of rigid-rod clusters. The effect of dominatingly attractive fibril-fibril interactions is discussed within the context of fibril clustering in Lewy body formation.

ACS Chemical Neuroscience, Jun 2, 2021

Cooperative binding is a key feature of metabolic pathways, signaling, and transport processes. I... more Cooperative binding is a key feature of metabolic pathways, signaling, and transport processes. It provides tight regulation over a narrow concentration interval of a ligand, thus enabling switching to be triggered by small concentration variations. The data presented in this work reveal strong positive cooperativity of α-synuclein binding to phospholipid membranes. Fluorescence cross-correlation spectroscopy, confocal microscopy, and cryo-TEM results show that in excess of vesicles α-synuclein does not distribute randomly but binds only to a fraction of all available vesicles. Furthermore, α-synuclein binding to a supported lipid bilayer observed with total internal reflection fluorescence microscopy displays a much steeper dependence of bound protein on total protein concentration than expected for independent binding. The same phenomenon was observed in the case of α-synuclein binding to unilamellar vesicles of sizes in the nm and μm range as well as to flat supported lipid bilayers, ruling out that nonuniform binding of the protein is governed by differences in membrane curvature. Positive cooperativity of α-synuclein binding to lipid membranes means that the affinity of the protein to a membrane is higher where there is already protein bound compared to a bare membrane. The phenomenon described in this work may have implications for α-synuclein function in synaptic transmission and other membrane remodeling events.

Quarterly Reviews of Biophysics, 2019

The aggregation of the 11 residue long NACore peptide segment of α-synuclein (68-GAVVTGVTAVA-78) ... more The aggregation of the 11 residue long NACore peptide segment of α-synuclein (68-GAVVTGVTAVA-78) has been investigated using a combination of cryogenic transmission electron microscopy (cryo-TEM), small-and wide-angle X-ray scattering, and spectroscopy techniques. The aqueous peptide solubility is pH dependent, and aggregation was triggered by a pH quench from pH 11.3 to approximately pH 8 or 6, where the average peptide net charge is weakly negative (pH 8), or essentially zero (pH 6). Cryo-TEM shows the presence of long and stiff fibrillar aggregates at both pH, that are built up from β-sheets, as demonstrated by circular dichroism spectroscopy and thioflavin T fluorescence. The fibrils are crystalline, with a wide angle X-ray diffraction pattern that is consistent with a previously determined crystal structure of NACore. Of particular note is the cryo-TEM observation of small globular shaped aggregates, of the order of a few nanometers in size, adsorbed onto the surface of already formed fibrils at pH 6. The fibrillation kinetics is slow, and occurs on the time scale of days. Similarly slow kinetics is observed at both pH, but slightly slower at pH 6, even though the peptide solubility is here expected to be lower. The observation of the small globular shaped aggregates, together with the associated kinetics, could be highly relevant in relation to mechanisms of secondary nucleation and oligomer formation in amyloid systems.

Biophysical Journal, Feb 1, 2023

Frontiers in Physiology, Dec 18, 2020

Amyloids are implicated in many diseases, and disruption of lipid membrane structures is consider... more Amyloids are implicated in many diseases, and disruption of lipid membrane structures is considered as one possible mechanism of pathology. In this paper we investigate interactions between an aggregating peptide and phospholipid membranes, focusing on the nanometer-scale structures of the aggregates formed, as well as on the effect on the aggregation process. As a model system, we use the small amyloid-forming peptide named NACore, which is a fragment of the central region of the protein α-synuclein that is associated with Parkinson's disease. We find that phospholipid vesicles readily associate with the amyloid fibril network in the form of highly distorted and trapped vesicles that also may wet the surface of the fibrils. This effect is most pronounced for model lipid systems containing only zwitterionic lipids. Fibrillation is found to be retarded by the presence of the vesicles. At the resolution of our measurements, which are based mainly on cryogenic transmission electron microscopy (cryo-TEM), X-ray scattering, and circular dichroism (CD) spectroscopy, we find that the resulting aggregates can be well fitted as linear combinations of peptide fibrils and phospholipid bilayers. There are no detectable effects on the cross-β packing of the peptide molecules in the fibrils, or on the thickness of the phospholipid bilayers. This suggests that while the peptide fibrils and lipid bilayers readily co-assemble on large length-scales, most of them still retain their separate structural identities on molecular length-scales. Comparison between this relatively simple model system and other amyloid systems might help distinguish aspects of amyloid-lipid interactions that are generic from aspects that are more protein specific. Finally, we briefly consider possible implications of the obtained results for in-vivo amyloid toxicity.

Physical Chemistry Chemical Physics, 2020

The outermost layer of the skin is the stratum corneum (SC), which is mainly comprised of solid p... more The outermost layer of the skin is the stratum corneum (SC), which is mainly comprised of solid proteins and lipids. Minor amounts of mobile proteins and lipids are crucial for the macroscopic properties of the SC, including softness, elasticity and barrier function. Still this minor number of mobile components are not well characterized in terms of structure or amount. Conventional quantitative direct polarization (Q-DP) 13 C solid-state NMR gives signal amplitudes proportional to concentrations, but fails to quantify the SC mobile components because of spectral overlap with the overwhelming signals from the solids. Spectral editing with the INEPT scheme suppresses the signals from solids, but also modulates the amplitudes of the mobile components depending on their values of the transverse relaxation times T 2 , scalar couplings J CH , and number of covalently bound hydrogens n H. This study describes a quantitative INEPT (Q-INEPT) method relying on systematic variation of the INEPT timing variables to estimate T 2 , J CH , n H , and amplitude for each of the resolved resonances from the mobile components. Q-INEPT is validated with a series of model systems containing molecules with different hydrophobicity and dynamics. For selected systems where Q-DP is applicable, the results of Q-INEPT and Q-DP are similar with respect to the linearity and uncertainty of the obtained molar ratios. Utilizing a reference compound with known concentration, we quantify the concentrations of mobile lipids and proteins within the mainly solid SC. By melting all lipids at high temperature, we obtain the total lipid concentration. These Q-INEPT results are the first steps towards a quantitative understanding of the relations between mobile component concentrations and SC macroscopic properties.

Frontiers in Molecular Neuroscience, Dec 1, 2022

Interactions of lipid vesicles play important roles in a large variety of functions and dysfuncti... more Interactions of lipid vesicles play important roles in a large variety of functions and dysfunctions in the human body. Vital for several biochemical functions is the interaction between monomeric proteins and lipid membranes, and the induced phenomena such as fusion between vesicles and cell membranes, lipid exchange between the membranes, or vesicle fission. Identification of single events and their frequency of occurrence would provide valuable information about protein-lipid interactions in both healthy and degenerative pathways. In this work, we present a single-vesicle intensity and colocalization fluorescence microscopy assay with a custom-written MATLAB analysis program. The assay can be used to study lipid exchange as well as vesicle fusion and fission between two vesicle populations labeled with different fluorescent dyes. Vesicles from the two populations are first mixed and docked to a glass surface. The sample is then simultaneously imaged using two separate wavelength channels monitoring intensity changes and colocalization of vesicles from the two populations. The monomeric pre-synaptic protein α-synuclein (α-syn) and small unilamellar vesicles consisting of 1,2-dioleoylsn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine, (DOPS), and monosialotetrahexosylganglioside (GM1) were used as a model system to evaluate the method. From our analysis, neither α-syn induced fusion nor lipid exchange was observed for vesicles consisting of DOPC:DOPS (7:3). However, including 10% GM1 in the vesicles resulted in a 91% increase of the number of vesicles within 10 min, combined with a 57% decrease in the average fluorescence intensity per vesicle, indicating that approximately half of the vesicles underwent fission. The method facilitates the study of lipid vesicle fusion, fission, and lipid exchange under controlled conditions. It also allows these events to be studied for systems with more complex composition including exosomes and lipid-based drug carriers, to enable a better understanding of their physicochemical properties.

Journal of Physical Chemistry Letters, Dec 2, 2019

The deposition of coassemblies made of the small presynaptic protein, α-synuclein, and lipids in ... more The deposition of coassemblies made of the small presynaptic protein, α-synuclein, and lipids in the brains of patients is the hallmark of Parkinson's disease. In this study, we used natural abundance 13 C and 31 P magic-angle spinning nuclear magnetic resonance spectroscopy together with cryo-electron microscopy and differential scanning calorimetry to characterize the fibrils formed by α-synuclein in the presence of vesicles made of 1,2-dimyristoyl-sn-glycero-3-phospho-Lserine or 1,2-dilauroyl-sn-glycero-3-phospho-L-serine. Our results show that these lipids coassemble with α-synuclein molecules to give thin and curly amyloid fibrils. The coassembly leads to slower and more isotropic reorientation of lipid molecular segments and a decrease in both the temperature and enthalpy of the lipid chain-melting compared with those in the protein-free lipid lamellar phase. These findings provide new insights into the properties of lipids within protein−lipid assemblies that can be associated with Parkinson's disease.

Journal of Controlled Release, Apr 1, 2010

Peptides with trypanocidal activity are promising compounds for the treatment of African Sleeping... more Peptides with trypanocidal activity are promising compounds for the treatment of African Sleeping Sickness, which have motivated the research into the ability of these compounds to disrupt the protozoan membrane. In this present study, we used the Langmuir monolayer technique to investigate the surface properties of an antiparasitic and zwitterionic peptide, namely S-(2,4-dinitrophenyl) glutathione di-2-propyl ester, and its interaction with a model membrane comprising a phospholipid monolayer, dipalmitoyl phosphatidyl choline (DPPC). The peptide formed a stable Langmuir monolayer, whose main feature of its surface pressure-area isotherm was the presence of a phase transition accompanied by a negative surface compressional modulus, which was attributed to the aggregation upon compression due to intermolecular bond associations of the molecules. This was inferred from surface pressure and surface potential isotherms, Brewster angle microscopy (BAM) images, Polarization modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS), and dynamic elasticity measurements by the pendant drop technique. When co-spread with dipalmitoyl phosphatidyl choline (DPPC), the drug affected both the surface pressure and the monolayer morphology, even at high surface pressures and with low amounts of the drug. The results were interpreted by assuming a repulsive, cooperative interaction between the drug and DPPC molecules. Such repulsive interaction and the large changes in fluidity arising from drug aggregation may be related to the disruption of the membrane, which is key for the parasite killing property.

Current Opinion in Colloid and Interface Science, Oct 1, 2023

International Journal of Molecular Sciences, Aug 7, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Springer eBooks, Apr 1, 2009

ABSTRACT

Proceedings of the National Academy of Sciences of the United States of America, Mar 1, 2019

Journal of Physical Chemistry B, Oct 27, 2006

Europe PMC (PubMed Central), 2013

Biochimica Et Biophysica Acta - Proteins And Proteomics, May 1, 2019

Lipid-protein interactions in amyloid formation Lipid membranes and amyloid fibrils are dynamic s... more Lipid-protein interactions in amyloid formation Lipid membranes and amyloid fibrils are dynamic self-assembled structures that co-exist in biology and have a clear influence on each other. The amyloid-forming protein may perturb the structure and integrity of the membrane (Fig. 1A), and the presence of the membrane may trigger the protein aggregation. Equally important, the coexistence of these dynamic systems of proteins and lipids, respectively, may lead to the formation of co-aggregates (Fig. 1B) that are lipid-rich or protein rich (Fig. 2). The main driving force for protein aggregation lies in the hydrophobic interactions, and amphiphilic molecules, such as membrane lipids, can interfere or even take part of such association process. Here, it is important to realise that the lipid membrane is a selfassembled dynamic structure rather than an intact and inert entity, and the amphiphilic lipids can rearrange into new assemblies together with other macromolecules when the conditions change. The co-assembly process may thus lead to that lipids from the membrane are taken up into the amyloid aggregates during their formation (Fig. 1B) [1-3]. Moreover, co-assembly in vivo occurs in an environment that contains many other substances, which potentially could take part in the process as physiologically relevant factors that

Journal of Colloid and Interface Science, Mar 1, 2023

Frontiers in Molecular Biosciences, Oct 19, 2021

The dense accumulation of α-Synuclein fibrils in neurons is considered to be strongly associated ... more The dense accumulation of α-Synuclein fibrils in neurons is considered to be strongly associated with Parkinson's disease. These intracellular inclusions, called Lewy bodies, also contain significant amounts of lipids. To better understand such accumulations, it should be important to study α-Synuclein fibril formation under conditions where the fibrils lump together, mimicking what is observed in Lewy bodies. In the present study, we have therefore investigated the overall structural arrangements of α-synuclein fibrils, formed under mildly acidic conditions, pH 5.5, in pure buffer or in the presence of various model membrane systems, by means of small-angle neutron scattering (SANS). At this pH, α-synuclein fibrils are colloidally unstable and aggregate further into dense clusters. SANS intensities show a power law dependence on the scattering vector, q, indicating that the clusters can be described as mass fractal aggregates. The experimentally observed fractal dimension was d 2.6 ± 0.3. We further show that this fractal dimension can be reproduced using a simple model of rigid-rod clusters. The effect of dominatingly attractive fibril-fibril interactions is discussed within the context of fibril clustering in Lewy body formation.

ACS Chemical Neuroscience, Jun 2, 2021

Cooperative binding is a key feature of metabolic pathways, signaling, and transport processes. I... more Cooperative binding is a key feature of metabolic pathways, signaling, and transport processes. It provides tight regulation over a narrow concentration interval of a ligand, thus enabling switching to be triggered by small concentration variations. The data presented in this work reveal strong positive cooperativity of α-synuclein binding to phospholipid membranes. Fluorescence cross-correlation spectroscopy, confocal microscopy, and cryo-TEM results show that in excess of vesicles α-synuclein does not distribute randomly but binds only to a fraction of all available vesicles. Furthermore, α-synuclein binding to a supported lipid bilayer observed with total internal reflection fluorescence microscopy displays a much steeper dependence of bound protein on total protein concentration than expected for independent binding. The same phenomenon was observed in the case of α-synuclein binding to unilamellar vesicles of sizes in the nm and μm range as well as to flat supported lipid bilayers, ruling out that nonuniform binding of the protein is governed by differences in membrane curvature. Positive cooperativity of α-synuclein binding to lipid membranes means that the affinity of the protein to a membrane is higher where there is already protein bound compared to a bare membrane. The phenomenon described in this work may have implications for α-synuclein function in synaptic transmission and other membrane remodeling events.

Quarterly Reviews of Biophysics, 2019

The aggregation of the 11 residue long NACore peptide segment of α-synuclein (68-GAVVTGVTAVA-78) ... more The aggregation of the 11 residue long NACore peptide segment of α-synuclein (68-GAVVTGVTAVA-78) has been investigated using a combination of cryogenic transmission electron microscopy (cryo-TEM), small-and wide-angle X-ray scattering, and spectroscopy techniques. The aqueous peptide solubility is pH dependent, and aggregation was triggered by a pH quench from pH 11.3 to approximately pH 8 or 6, where the average peptide net charge is weakly negative (pH 8), or essentially zero (pH 6). Cryo-TEM shows the presence of long and stiff fibrillar aggregates at both pH, that are built up from β-sheets, as demonstrated by circular dichroism spectroscopy and thioflavin T fluorescence. The fibrils are crystalline, with a wide angle X-ray diffraction pattern that is consistent with a previously determined crystal structure of NACore. Of particular note is the cryo-TEM observation of small globular shaped aggregates, of the order of a few nanometers in size, adsorbed onto the surface of already formed fibrils at pH 6. The fibrillation kinetics is slow, and occurs on the time scale of days. Similarly slow kinetics is observed at both pH, but slightly slower at pH 6, even though the peptide solubility is here expected to be lower. The observation of the small globular shaped aggregates, together with the associated kinetics, could be highly relevant in relation to mechanisms of secondary nucleation and oligomer formation in amyloid systems.

Biophysical Journal, Feb 1, 2023

Frontiers in Physiology, Dec 18, 2020

Amyloids are implicated in many diseases, and disruption of lipid membrane structures is consider... more Amyloids are implicated in many diseases, and disruption of lipid membrane structures is considered as one possible mechanism of pathology. In this paper we investigate interactions between an aggregating peptide and phospholipid membranes, focusing on the nanometer-scale structures of the aggregates formed, as well as on the effect on the aggregation process. As a model system, we use the small amyloid-forming peptide named NACore, which is a fragment of the central region of the protein α-synuclein that is associated with Parkinson's disease. We find that phospholipid vesicles readily associate with the amyloid fibril network in the form of highly distorted and trapped vesicles that also may wet the surface of the fibrils. This effect is most pronounced for model lipid systems containing only zwitterionic lipids. Fibrillation is found to be retarded by the presence of the vesicles. At the resolution of our measurements, which are based mainly on cryogenic transmission electron microscopy (cryo-TEM), X-ray scattering, and circular dichroism (CD) spectroscopy, we find that the resulting aggregates can be well fitted as linear combinations of peptide fibrils and phospholipid bilayers. There are no detectable effects on the cross-β packing of the peptide molecules in the fibrils, or on the thickness of the phospholipid bilayers. This suggests that while the peptide fibrils and lipid bilayers readily co-assemble on large length-scales, most of them still retain their separate structural identities on molecular length-scales. Comparison between this relatively simple model system and other amyloid systems might help distinguish aspects of amyloid-lipid interactions that are generic from aspects that are more protein specific. Finally, we briefly consider possible implications of the obtained results for in-vivo amyloid toxicity.

Physical Chemistry Chemical Physics, 2020

The outermost layer of the skin is the stratum corneum (SC), which is mainly comprised of solid p... more The outermost layer of the skin is the stratum corneum (SC), which is mainly comprised of solid proteins and lipids. Minor amounts of mobile proteins and lipids are crucial for the macroscopic properties of the SC, including softness, elasticity and barrier function. Still this minor number of mobile components are not well characterized in terms of structure or amount. Conventional quantitative direct polarization (Q-DP) 13 C solid-state NMR gives signal amplitudes proportional to concentrations, but fails to quantify the SC mobile components because of spectral overlap with the overwhelming signals from the solids. Spectral editing with the INEPT scheme suppresses the signals from solids, but also modulates the amplitudes of the mobile components depending on their values of the transverse relaxation times T 2 , scalar couplings J CH , and number of covalently bound hydrogens n H. This study describes a quantitative INEPT (Q-INEPT) method relying on systematic variation of the INEPT timing variables to estimate T 2 , J CH , n H , and amplitude for each of the resolved resonances from the mobile components. Q-INEPT is validated with a series of model systems containing molecules with different hydrophobicity and dynamics. For selected systems where Q-DP is applicable, the results of Q-INEPT and Q-DP are similar with respect to the linearity and uncertainty of the obtained molar ratios. Utilizing a reference compound with known concentration, we quantify the concentrations of mobile lipids and proteins within the mainly solid SC. By melting all lipids at high temperature, we obtain the total lipid concentration. These Q-INEPT results are the first steps towards a quantitative understanding of the relations between mobile component concentrations and SC macroscopic properties.

Frontiers in Molecular Neuroscience, Dec 1, 2022

Interactions of lipid vesicles play important roles in a large variety of functions and dysfuncti... more Interactions of lipid vesicles play important roles in a large variety of functions and dysfunctions in the human body. Vital for several biochemical functions is the interaction between monomeric proteins and lipid membranes, and the induced phenomena such as fusion between vesicles and cell membranes, lipid exchange between the membranes, or vesicle fission. Identification of single events and their frequency of occurrence would provide valuable information about protein-lipid interactions in both healthy and degenerative pathways. In this work, we present a single-vesicle intensity and colocalization fluorescence microscopy assay with a custom-written MATLAB analysis program. The assay can be used to study lipid exchange as well as vesicle fusion and fission between two vesicle populations labeled with different fluorescent dyes. Vesicles from the two populations are first mixed and docked to a glass surface. The sample is then simultaneously imaged using two separate wavelength channels monitoring intensity changes and colocalization of vesicles from the two populations. The monomeric pre-synaptic protein α-synuclein (α-syn) and small unilamellar vesicles consisting of 1,2-dioleoylsn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine, (DOPS), and monosialotetrahexosylganglioside (GM1) were used as a model system to evaluate the method. From our analysis, neither α-syn induced fusion nor lipid exchange was observed for vesicles consisting of DOPC:DOPS (7:3). However, including 10% GM1 in the vesicles resulted in a 91% increase of the number of vesicles within 10 min, combined with a 57% decrease in the average fluorescence intensity per vesicle, indicating that approximately half of the vesicles underwent fission. The method facilitates the study of lipid vesicle fusion, fission, and lipid exchange under controlled conditions. It also allows these events to be studied for systems with more complex composition including exosomes and lipid-based drug carriers, to enable a better understanding of their physicochemical properties.

Journal of Physical Chemistry Letters, Dec 2, 2019

The deposition of coassemblies made of the small presynaptic protein, α-synuclein, and lipids in ... more The deposition of coassemblies made of the small presynaptic protein, α-synuclein, and lipids in the brains of patients is the hallmark of Parkinson's disease. In this study, we used natural abundance 13 C and 31 P magic-angle spinning nuclear magnetic resonance spectroscopy together with cryo-electron microscopy and differential scanning calorimetry to characterize the fibrils formed by α-synuclein in the presence of vesicles made of 1,2-dimyristoyl-sn-glycero-3-phospho-Lserine or 1,2-dilauroyl-sn-glycero-3-phospho-L-serine. Our results show that these lipids coassemble with α-synuclein molecules to give thin and curly amyloid fibrils. The coassembly leads to slower and more isotropic reorientation of lipid molecular segments and a decrease in both the temperature and enthalpy of the lipid chain-melting compared with those in the protein-free lipid lamellar phase. These findings provide new insights into the properties of lipids within protein−lipid assemblies that can be associated with Parkinson's disease.

Journal of Controlled Release, Apr 1, 2010

Peptides with trypanocidal activity are promising compounds for the treatment of African Sleeping... more Peptides with trypanocidal activity are promising compounds for the treatment of African Sleeping Sickness, which have motivated the research into the ability of these compounds to disrupt the protozoan membrane. In this present study, we used the Langmuir monolayer technique to investigate the surface properties of an antiparasitic and zwitterionic peptide, namely S-(2,4-dinitrophenyl) glutathione di-2-propyl ester, and its interaction with a model membrane comprising a phospholipid monolayer, dipalmitoyl phosphatidyl choline (DPPC). The peptide formed a stable Langmuir monolayer, whose main feature of its surface pressure-area isotherm was the presence of a phase transition accompanied by a negative surface compressional modulus, which was attributed to the aggregation upon compression due to intermolecular bond associations of the molecules. This was inferred from surface pressure and surface potential isotherms, Brewster angle microscopy (BAM) images, Polarization modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS), and dynamic elasticity measurements by the pendant drop technique. When co-spread with dipalmitoyl phosphatidyl choline (DPPC), the drug affected both the surface pressure and the monolayer morphology, even at high surface pressures and with low amounts of the drug. The results were interpreted by assuming a repulsive, cooperative interaction between the drug and DPPC molecules. Such repulsive interaction and the large changes in fluidity arising from drug aggregation may be related to the disruption of the membrane, which is key for the parasite killing property.

Current Opinion in Colloid and Interface Science, Oct 1, 2023

International Journal of Molecular Sciences, Aug 7, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Springer eBooks, Apr 1, 2009

ABSTRACT

Proceedings of the National Academy of Sciences of the United States of America, Mar 1, 2019

Journal of Physical Chemistry B, Oct 27, 2006

Europe PMC (PubMed Central), 2013