Stem Cell Therapy for Myocardial Infarction and Heart Failure: A Comprehensive Systematic Review and Critical Analysis.

In exploring therapeutic options for ischemic heart disease (IHD) and heart failure, cell-based cardiac repair has gained prominence. This systematic review delves into the current state of knowledge surrounding cell-based therapies for cardiac repair. Employing a comprehensive search across relevant databases, the study identifies 35 included studies with diverse cell types and methodologies. Encouragingly, these findings reveal the promise of cell-based therapies in cardiac repair, demonstrating significant enhancements in left ventricular ejection fraction (LVEF) across the studies. Mechanisms of action involve growth factors that stimulate angiogenesis, differentiation, and the survival of transplanted cells. Despite these positive outcomes, challenges persist, including low engraftment rates, limitations in cell differentiation, and variations in clinical reproducibility. The optimal dosage and frequency of cell administration remain subjects of debate, with potential benefits from repeated dosing. Additionally, the choice between autologous and allogeneic stem cell transplantation poses a critical decision. This systematic review underscores the potential of cell-based therapies for cardiac repair, bearing implications for innovative treatments in heart diseases. However, further research is imperative to optimize cell type selection, delivery techniques, and long-term efficacy, fostering a more comprehensive understanding of cell-based cardiac repair.

Methotrexate-Induced Mucositis: A Consequence of Medication Error in a Rheumatoid Arthritis Patient.

Methotrexate (MTX) is a commonly prescribed medication for the treatment of rheumatoid arthritis (RA). Although effective in managing rheumatoid arthritis symptoms, methotrexate can have adverse effects, including mucositis. This study highlights a case of methotrexate-induced mucositis resulting from a medication error in a patient with rheumatoid arthritis. The 69-year-old patient recently diagnosed with rheumatoid arthritis was receiving methotrexate therapy as a part of his treatment plan. The patient, however, unintentionally ingested an excessive dose of methotrexate because of a communication error that occurred during the medication administration process. He started displaying signs of oral mucositis, characterized by uncomfortable ulcers and oral mucosa inflammation, within a short period. The buccal mucosa, tongue, and gingiva of the patient's oral cavity displayed numerous ulcerative lesions upon examination. Due to the mucositis's severity, it was challenging to eat, speak, and perform regular oral hygiene procedures. The patient described severe discomfort that had a detrimental effect on his general quality of life. This case serves as a reminder of the importance of accurate medication administration and communication in the management of rheumatoid arthritis. Healthcare professionals should ensure proper dosing and monitoring to minimize the risk of medication errors and associated complications. Additionally, patients should be educated about the potential side effects of methotrexate, including mucositis, to enable early recognition and timely intervention. In conclusion, this study emphasizes the occurrence of methotrexate-induced mucositis because of medication administration errors in a patient with rheumatoid arthritis. By increasing awareness of this potential complication, healthcare providers can improve patient safety and enhance the overall management of rheumatoid arthritis treatment.

Photocatalytic activity of biosynthesized silver nanoparticle fosters oxidative stress at nanoparticle interface resulting in antimicrobial and cytotoxic activities.

Inside the biological milieu, nanoparticles with photocatalytic activity have potential to trigger cell death non-specifically due to production of reactive oxygen species (ROS) upon reacting with biological entities. Silver nanoparticle (AgNP) possessing narrow band gap energy can exhibit high light absorption property and significant photocatalytic activity. This study intends to explore the effects of ROS generated due to photocatalytic activity of AgNP on antimicrobial and cytotoxic propensities. To this end, AgNP was synthesized using the principle of green chemistry from the peel extract of Punica granatum L., and was characterized using UV-Vis spectroscope, transmission electron microscope and x-ray diffraction, and so forth. The antimicrobial activity of AgNP against studied bacteria indicated that, ROS generated at AgNP interface develop stress on bacterial membrane leading to bacterial cell death, whereas Alamar Blue dye reduction assay indicated that increased cytotoxic activity with increasing concentrations of AgNP. The γH2AX activity assay revealed that increasing the concentrations of AgNP increased DNA damaging activity. The results altogether demonstrated that both antimicrobial and cytotoxic propensities are triggered primarily due interfacial ROS generation by photocatalytic AgNP, which caused membrane deformation in bacteria and DNA damage in HT1080 cells resulting in cell death.

Multiple Hepatic Abscesses Secondary to Streptococcus anginosus Infection: A Case Report and Review of the Literature.

Hepatic abscesses are rare and generally present as solitary lesions in immunocompromised patients. The development of multiple hepatic abscesses in an immunocompetent patient is relatively uncommon. We report a rare case of a 73-year-old woman who presented with fever and right upper quadrant abdominal tenderness. Laboratory findings were significant for leukocytosis, transaminitis, and elevated inflammatory markers. Peripheral blood culture grew Streptococcus anginosus. Computed tomography of the abdomen and pelvis (CT A/P) revealed multiple hypoattenuating ill-defined cystic lesions in the liver consistent with abscesses formation; this was confirmed by magnetic resonance cholangiopancreatography (MRCP). The patient underwent appropriate treatment with antibiotics. Upon a three-week follow-up, the patient's symptoms subsided, and her laboratory parameters normalized. Although Streptococcus anginosus is a normal gastrointestinal flora, it has the potential to form abscesses. Our report indicates the importance of considering Streptococcus anginosus in the differential diagnosis. Management includes four to six weeks of antibiotic therapy together with drainage of larger abscesses.

Spectroscopic and molecular docking studies for the binding and interaction aspects of curcumin-cysteine conjugate and rosmarinic acid with human telomeric G-quadruplex DNA.

The binding and interaction aspects of potential anticancer ligands like: curcumin-cysteine (CC) and rosmarinic acid (RA) with human telomeric G-quadruplex DNA, a novel anticancer target, have been probed by spectroscopic and molecular docking approach. The circular dichroism study unravels the conformational switching from mixed hybrid to parallel structure for the short sequence of human telomeric G-quadruplex structure in the presence of both the ligands. Further a good correlation for binding affinity has been established from the emission and absorption binding spectrum analysis. Further our spectroscopic and molecular docking studies have suggested that the CC having better binding capability than RA to human telomeric G-quadruplex. The presence of L-cysteine moiety in CC ligand is responsible factor for its binding via both minor as well as major groove of human telomeric G-quadruplex DNA where-as RA binds only via minor groove of telomeric G-DNA.

Interaction with zinc oxide nanoparticle kinetically traps α-synuclein fibrillation into off-pathway non-toxic intermediates.

α-Synuclein is an intrinsically disordered amyloidogenic protein associated with Parkinson's disease (PD). The monomeric α-synuclein transition into amyloid fibril involves multiple steps, which are affected by several intrinsic and extrinsic factors. This increases complexities in development of targeted therapeutics against the pathological intermediate(s). Several studies have been dedicated to find an effective molecule to inhibit the detrimental amyloidogenesis. In recent years, metal oxide nanoparticle interfaces have shown direct effects on protein conformation, hence may be adopted as an alternative potential therapeutic approach against amyloidosis. In this context, our study explores the zinc oxide nanoparticle (ZnONP) with negative surface potential interface interaction with α-synuclein, and subsequent impact of the interaction on the protein fibrillation and the fibril-mediated cytotoxicity. N-terminus amphipathic "KA/TKE/QGV" repeating motifs in α-synuclein primarily interact with the ZnONP interface that enthalpically drives initial adsorption of the protein onto the interface. Whereas, subsequent bulk-protein adsorption onto the hard-corona is entropically driven, leading into flocculation of the complex. The flocs appear as amorphous mesh-like morphology in TEM micrographs, as opposed to the typical fibrils formed by the wild-type protein. Interestingly, α-synuclein in complex with ZnONP shows significantly lowered cytotoxicity against the IMR32 and THP-1 cells in-vitro, as compared to fresh α-synuclein.

Silver nanoparticles fabricated using medicinal plant extracts show enhanced antimicrobial and selective cytotoxic propensities.

Nanoparticles fabricated using medicinal plant extract have great potential in the area of nanomedicine. High surface-to-volume ratio of nanoparticle enhances the local active biomolecules concentration, leading to many fold increase in the medicinal potentials. The silver nanoparticles (AgNPs) fabricated using indigenous medicinal plants of India, Azadirachta indica and Syzygium cumini, have shown a significant effect on the viability of prokaryotic and eukaryotic cells. Biofabrication of AgNP was confirmed using different spectroscopic and microscopic techniques. Extraction and purification of AgNP from non-conjugated plant moieties are done using centrifugation and size exclusion chromatography. The cytotoxic propensity of AgNP formulations was screened against Gram-positive (Bacillus subtilis), Gram-negative (Escherichia coli) bacteria, cancerous (HT1080) and non-cancerous (HEK293) cell lines. The nanoparticle formulations showed a relatively higher cytotoxic propensity against Gram-positive bacteria and cancerous cell lines. In addition, the surface roughness and reactive oxygen species (ROS) measurements indicated that AgNP formulations mediate the cell activity predominantly by ROS-mediated disruptive change in membrane morphology upon direct interaction with the membrane. Hence, the nanoparticle formulations show an enhanced selective cytotoxic propensity towards Gram-positive bacteria and cancerous cell lines.

Attenuation of neuroblastoma cell growth by nisin is mediated by modulation of phase behavior and enhanced cell membrane fluidity.

Antimicrobial peptides have been attracting significant attention as potential anti-cancer therapeutic agents in recent times. Yet most antimicrobial peptides seem to possess cytotoxic effects on non-cancerous cells. Nisin, an antimicrobial peptide and FDA approved food preservative, has recently been found to induce selective apoptotic cell death and reduced cell proliferation in different cancer cell lines. However, the mechanism of nisin interaction with cancer cell membranes remains unexplored. Using potentiometric dye-based fluorescence and monolayer surface pressure-area isotherms we find that nisin interaction enhances the fluidity and reduces the dipole potential of a neuroblastoma cell membrane model. The quantified compressibility modulus suggests that the changes in fluidity are predominantly driven by the nisin interaction with the non-raft like regions. However, the measured positive Gibbs free energy of mixing and enthalpy hints that nisin, owing to its unfavorable mixing with cholesterol, might significantly disrupt the raft-like domains.

Oxidative stress generated at nickel oxide nanoparticle interface results in bacterial membrane damage leading to cell death.

Metal oxide nanoparticles (NPs) have shown enhanced antibacterial effects against many bacteria. Thus, understanding the potential antibacterial effects of nickel oxide nanoparticles (NiO NPs) against Gram-positive and Gram-negative pathogenic bacteria is an urgent need to enable the exploration of NiO NP use in biomedical sciences. To this end, NiO NPs were synthesized by microwave assisted hydrothermal synthesis method. The synthesized NPs were characterized by X-ray diffraction (XRD) and Fourier Transfer Infrared (FT-IR) and UV-visible spectroscopy. The morphological features of the synthesized NiO NPs were analysed using Transmission Electron Microscopy (TEM) and FE-SEM analysis. The antibacterial activity of NiO NP was explored using different antimicrobial and biophysical studies. The obtained data reveals that the NiO NP has stronger antibacterial activity against Gram-positive bacteria compared to Gram-negative bacteria. The mechanism behind the antibacterial activity of the NiO NP was explored by evaluating the amount of ROS generation at the NiO NP interface. The effect of ROS generation on the bacterial membrane was evaluated by BacLight assay and morphological analysis of the bacterial membrane using FE-SEM. The data altogether suggested that the oxidative stress generated at the NiO NP interface resulted in membrane damage leading to bacterial cell death.

Insulin adsorption onto zinc oxide nanoparticle mediates conformational rearrangement into amyloid-prone structure with enhanced cytotoxic propensity.

BACKGROUND: Injection localized amyloidosis is one of the most prevalent disorders in type II diabetes mellitus (TIIDM) patients relying on insulin injections. Previous studies have reported that nanoparticles can play a role in the amyloidogenic process of proteins. Hence, the present study deals with the effect of zinc oxide nanoparticles (ZnONP) on the amyloidogenicity and cytotoxicity of insulin. METHODS: ZnONP is synthesised and characterized using XRD, Zeta Sizer, UV-Visible spectroscope and TEM. The characterization is followed by ZnONP interaction with insulin, which is studied employing fluorescence spectroscopes, isothermal titration calorimetry and molecular dynamics simulations. The interaction leads insulin conformational rearrangement into amyloid-like fibril, which is studied using thioflavin T dye binding assay, circular dichroism spectroscopy and TEM, followed by cytotoxicity propensity using Alamar Blue dye reduction assay. RESULTS: Insulin has very weak interaction with ZnONP interface. Insulin at studied concentration forms amorphous aggregates at physiological pH, whereas in presence of ZnONP interface amyloid-like fibrils are formed. While the amyloid-like fibrils are cytotoxic to MIN6 and THP-1 cell lines, insulin and ZnONP individual solutions and their fresh mixtures enhance the cells proliferation. CONCLUSIONS: The presence of ZnONP interface enhances insulin fibrillation at physiological pH by providing a favourable template for the nucleation and growth of insulin amyloids. GENERAL SIGNIFICANCE: The studied protein-nanoparticle system from protein conformational dynamics point of view throws caution over nanoparticle use in biological applications, especially in vivo applications, considering the amyloidosis a very slow but non-curable degenerative disease.

Preferential binding to zinc oxide nanoparticle interface inhibits lysozyme fibrillation and cytotoxicity.

The aim of present investigation is to explore the effect of zinc oxide nanoparticles (ZnONP, 30 nm) interface on conformational dynamics and stability of lysozyme, at pH 7.4 and pH 9.0. Lysozyme adopts partially disordered conformation at pH 9.0, which adopts fibril morphology in presence of sodium dodecyl sulfate (SDS), compared to the conformation adopted at pH 7.4. However, the presence of ZnONP interface renders partially disordered lysozyme relatively regular and non-amyloidogenic conformation, and enhances the functional efficacy of lysozyme at pH 9.0. Additionally, the thermograms reveal a non-cooperative unfolding of the pH 9.0 lysozyme conformation, which accompanied with intermediate conformations that increased with increase in the interface concentration. The binding thermodynamics indicate that at pH 9.0, lysozyme conformation preferentially binds to ZnONP interface than SDS interface. The preferential binding is attributed for the resulting anti-fibrillation propensity of ZnONP interface. The data, altogether, suggest that the presence of ZnONP interface resulted in conformational rearrangements in the partially disordered lysozyme at pH 9.0 causing accumulation of non-amyloidogenic and functionally active intermediates, thus shielding the lysozyme from SDS induced fibrillation and cytotoxicity.

The smaller heparin fragments bind non-specifically through the IAPP sequence: An in silico study.

The diminishing ß-cell mass of pancreas in type II diabetes mellitus (TIIDM) is intricately linked with high fibrillation propensity of islet amyloid polypeptide (IAPP, aka amylin). IAPP is one of the most amyloidogenic peptide secreted by pancreatic ß-cells. In the autopsy of TIIDM patients, IAPP rich amyloid plaques are found containing different components of extracellular matrix (ECM), including heparin. For a positively charged IAPP, interaction with heparin which has accessible high density negatively charged functional groups is anticipated to moderate the fibrillation kinetics. Hence, the heparin has shown to affect the amyloidogenicity and cytotoxicity of IAPP depending upon its polymer length; short polymer inhibited the amyloidogenicity and longer fragment enhanced the propensity. Here using docking and molecular dynamic (MD) simulations studies, the work investigates key interactions between IAPP and different heparin fragments, those are likely involved in moderating IAPP fibrillation kinetics in presence of different length heparin fragments. The findings indicate that the heparin fragments of longer length, >dp7, predominantly interact with IAPP N- and C-termini, resulting in a stable complex with solvent accessible self-recognition element (SRE) of IAPP sequence. However, shorter fragment non-specifically binds through the IAPP sequence, including N-terminus residues and SRE sequences.

IAPP in type II diabetes: Basic research on structure, molecular interactions, and disease mechanisms suggests potential intervention strategies.

Islet amyloid polypeptide (a.k.a. IAPP, amylin) is a 37 amino acid hormone that has long been associated with the progression of type II diabetes mellitus (TIIDM) disease. The endocrine peptide hormone aggregatively misfolds to form amyloid deposits in and around the pancreatic islet ß-cells that synthesize both insulin and IAPP, leading to a decrease in ß-cell mass in patients with the disease. Extracellular IAPP amyloids induce ß-cell death through the formation of reactive oxygen species, mitochondrial dysfunction, chromatin condensation, and apoptotic mechanisms, although the precise roles of IAPP in TIIDM are yet to be established. Here we review aspects of the normal physiological function of IAPP in glucose regulation together with insulin, and its misfolding which contributes to TIIDM, and may also play roles in other pathologies such as Alzheimer's and heart disease. We summarize information on expression of the IAPP gene, the regulation of the hormone by post-translational modifications, the structural properties of the peptide in various states, the kinetics of misfolding to amyloid fibrils, and the interactions of the peptide with insulin, membranes, glycosaminoglycans, and nanoparticles. Finally, we describe how basic research is starting to have a positive impact on the development of approaches to circumvent IAPP amyloidogenesis. These include therapeutic strategies aimed at stabilizing non-amyloidogenic states, inhibition of amyloid growth or disruption of amyloid fibrils, antibodies directed towards amyloid structures, and inhibition of interactions with cofactors that facilitate aggregation or stabilize amyloids.

Zinc oxide nanoparticle energy band gap reduction triggers the oxidative stress resulting into autophagy-mediated apoptotic cell death.

The physico-chemical properties of nanoparticle (NP), such as particle size, surface defects, crystallinity and accessible surface, affect NP photocatalytic activity that in turn defines the NP cytotoxic propensity. Since zinc oxide nanoparticle (ZnONP) energy band gap falls in a range of a semiconductor, the particle possesses photocatalytic activity. Hence, the study correlates energy band gap with cytotoxic propensity of ZnONP. To this end, ZnONPs with varying energy band gap are fabricated by varying calcination temperature. Cytotoxic propensity of the fabricated ZnONPs against HT1080 cell indicates that the particle with least energy band gap shows highest cytotoxicity. The data also indicate that the cytotoxicity is triggered primarily through reactive oxygen species (ROS)-mediated pathway. Additionally, the comet assay and γH2AX activity assay reveal that decreasing energy band gap of the particle increases DNA damaging propensity. Furthermore, cell cycle analysis indicates that the cell treatment with decreasing energy band gap ZnONP results in significant increase in cell population fraction in subG1 phase. Whereas, acridine orange binding assay and increased expression level of LC3II indicate that the cell tries to recover the stress by scavenging damaged cellular biomolecules and ROS using autophagosomes. Nevertheless, cell with the non-recoverable damages led into apoptotic cell death, as confirmed by Annexin V apoptosis assay, DNA fragmentation assay and 4,6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining.

Antimicrobial activity of iron oxide nanoparticle upon modulation of nanoparticle-bacteria interface.

Investigating the interaction patterns at nano-bio interface is a key challenge for safe use of nanoparticles (NPs) to any biological system. The study intends to explore the role of interaction pattern at the iron oxide nanoparticle (IONP)-bacteria interface affecting antimicrobial propensity of IONP. To this end, IONP with magnetite like atomic arrangement and negative surface potential (n-IONP) was synthesized by co-precipitation method. Positively charged chitosan molecule coating was used to reverse the surface potential of n-IONP, i.e. positive surface potential IONP (p-IONP). The comparative data from fourier transform infrared spectroscope, XRD, and zeta potential analyzer indicated the successful coating of IONP surface with chitosan molecule. Additionally, the nanocrystals obtained were found to have spherical size with 10-20 nm diameter. The BacLight fluorescence assay, bacterial growth kinetic and colony forming unit studies indicated that n-IONP (<50 µM) has insignificant antimicrobial activity against Bacillus subtilis and Escherichia coli. However, coating with chitosan molecule resulted significant increase in antimicrobial propensity of IONP. Additionally, the assay to study reactive oxygen species (ROS) indicated relatively higher ROS production upon p-IONP treatment of the bacteria. The data, altogether, indicated that the chitosan coating of IONP result in interface that enhances ROS production, hence the antimicrobial activity.

pH dependence of amylin fibrillization.

In type 2 diabetics, the hormone amylin misfolds into amyloid plaques implicated in the destruction of the pancreatic ß-cells that make insulin and amylin. The aggregative misfolding of amylin is pH-dependent, and exposure of the hormone to acidic and basic environments could be physiologically important. Amylin has two ionizable residues between pH 3 and 9: the α-amino group and His18. Our approach to measuring the pKa values for these sites has been to look at the pH dependence of fibrillization in amylin variants that have only one of the two groups. The α-amino group at the unstructured N-terminus of amylin has a pKa near 8.0, similar to the value in random coil models. By contrast, His18, which is involved in the intermolecular ß-sheet structure of the fibrils, has a pKa that is lowered to 5.0 in the fibrils compared to the random coil value of 6.5. The lowered pKa of His18 is due to the hydrophobic environment of the residue, and electrostatic repulsion between positively charged His18 residues on neighboring amylin molecules in the fibril. His18 acts as an electrostatic switch inhibiting fibrillization in its charged state. The presence of a charged side chain at position 18 also affects fibril morphology and lowers amylin cytotoxicity toward a MIN6 mouse model of pancreatic ß-cells. In addition to the two expected pKa values, we detected an apparent pKa of ~4.0 for the amylin-derived peptide NAc-SNNFGAILSS-NH2, which has no titratable groups. This pKa is due to the pH-induced ionization of the dye thioflavin T. By using alternative methods to follow fibrillization such as the dye Nile Red or turbidimetry, we were able to distinguish between the titration of the dye and groups on the peptide. Large differences in reaction kinetics were observed between the different methods at acidic pH, because of charges on the ThT dye, which hinder fibril formation much like the charges on the protein.

Mechanism of amylin fibrillization enhancement by heparin.

We characterized the interaction of amylin with heparin fragments of defined length, which model the glycosaminoglycan chains associated with amyloid deposits found in type 2 diabetes. Binding of heparin fragments to the positively charged N-terminal half of monomeric amylin depends on the concentration of negatively charged saccharides but is independent of oligosaccharide length. By contrast, amylin fibrillogenesis has a sigmoidal dependence on heparin fragment length, with an enhancement observed for oligosaccharides longer than four monomers and a leveling off of effects beyond 12 monomers. The length dependence suggests that the negatively charged helical structure of heparin electrostatically complements the positively charged surface of the fibrillar amylin cross-ß structure. Fluorescence resonance energy transfer and total internal reflection fluorescence microscopy experiments indicate that heparin associates with amylin fibrils, rather than enhancing fibrillogenesis catalytically. Short heparin fragments containing two- or eight-saccharide monomers protect against amylin cytotoxicity toward a MIN6 mouse cell model of pancreatic ß-cells.

Heterogeneous amylin fibril growth mechanisms imaged by total internal reflection fluorescence microscopy.

Total internal reflection fluorescence microscopy has been used to visualize the fibrillization of amylin, a hormone which in aggregated forms plays a role in type 2 diabetes pathology. Data were obtained at acidic pH where fibrillization is hindered by the charging of histidine 18 and at slightly basic pH where the loss of charge on the histidine promotes aggregation. The experiments show three types of aggregate growth processes. In the earliest steps globular seeds are formed with some expanding radially during the course of the reaction. The dimensions of the globular seeds as well as their staining with the amyloid-specific dye thioflavin T indicate that they are plaques of short fibrils. The next species observed are fibrils that invariably grow from large globular seeds or smaller punctate granules. Fibril elongation appears to be unidirectional, although in some cases multiple fibrils radiate from a single seed or granule. After fibrils are formed, some show an increase in fluorescence intensity that we attribute to the growth of new fibrils alongside those previously formed. All three aggregation processes are suggestive of secondary (heterogeneous) nucleation mechanisms in which nucleation occurs on preformed fibrils. Consistently, electron micrographs show changes in fibril morphology well after fibrils are first formed, and the growth processes observed by fluorescence microscopy occur after the corresponding solution reactions have reached an initial apparent plateau. Taken together, the results highlight the importance of secondary nucleation in the fibrillization of amylin, as this could provide a pathway to continue fibril growth once an initial population of fibrils is established.

Amyloidogenic propensities and conformational properties of ProIAPP and IAPP in the presence of lipid bilayer membranes.

Human islet amyloid polypeptide (hIAPP), which is considered the primary culprit for beta-cell loss in type 2 diabetes mellitus patients, is synthesized in beta-cells of the pancreas from its precursor pro-islet amyloid polypeptide (proIAPP), which may be important in early intracellular amyloid formation as well. We compare the amyloidogenic propensities and conformational properties of proIAPP and hIAPP in the presence of negatively charged lipid membranes, which have been discussed as loci of initiation of the fibrillation reaction. Circular dichroism studies verify the initial secondary structures of proIAPP and hIAPP to be predominantly unordered with small amounts of ordered secondary structure elements, and exhibit minor differences between these two peptides only. Using attenuated total reflection-Fourier transform infrared spectroscopy and thioflavin T fluorescence spectroscopy, as well as atomic force microscopy, we show that in the presence of negatively charged membranes, proIAPP exhibits a much higher amyloidogenic propensity than in bulk solvent. Compared to hIAPP, it is still much less amyloidogenic, however. Although differences in the secondary structures of the aggregated species of hIAPP and proIAPP at the lipid interface are small, they are reflected in morphological changes. Unlike hIAPP, proIAPP forms essentially oligomeric-like structures at the lipid interface. Besides the interaction with anionic membranes [1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)+x1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)]], interaction with zwitterionic homogeneous (DOPC) and heterogeneous (1,2-dipalmitoyl-sn-glycero-3-phosphocholine:DOPC:cholesterol 1:2:1 model raft mixture) membranes has also been studied. Both peptides do not aggregate significantly at DOPC bilayers. In the presence of the model raft membrane, hIAPP aggregates markedly as well. Conversely, proIAPP clusters into less ordered structures and to a minor extent at raft membranes only. The addition of proIAPP to hIAPP retards the hIAPP fibrillation process also in the presence of negatively charged lipid bilayers. In excess proIAPP, increased aggregation levels are finally observed, however, which could be attributed to seed-induced cofibrillation of proIAPP.