Interaction Of Surfactant Protein Research Articles

Binding dynamics of linear alkyl-sulfates of different chain lengths on a protein surface

Sulfate-based anionic surfactants, such as sodium dodecyl sulfate (SDS), are widely recognized for their ability to deactivate and denature proteins. Despite extensive research, the molecular mechanisms governing the preferential binding of surfactants to protein surfaces remain incompletely understood. This study employs molecular dynamics (MD) simulations to investigate interactions between subtilisin E (SubE) and two anionic surfactants: SDS and sodium hexyl sulfate (SHS), with SHS possessing alkyl chains half the length of SDS. Simulations conducted at a low surfactant concentration (0.5% w/v) reveal distinct binding dynamics and interaction preferences of these surfactants with the SubE protein surface. Results demonstrate that the presence of SDS and SHS does not induce significant alterations in the overall secondary structure of SubE compared to simulations in pure water. The residue-level analysis identifies SDS as having greater contact with surface residues than SHS, particularly in helical and turn regions of SubE. SDS exhibits persistent binding sites in proximity to active site residues, suggesting potential implications for the observed experimental reduction in enzymatic activity. Dynamic interaction analysis indicates rapid and sustained binding of nearly all surfactant molecules to the protein within the initial 10-25 ns, with SDS displaying more transient interactions compared to SHS. Specific interaction patterns are observed between SDS and catalytic triad residues Asp32, His64, and Ser221, as well as Asn155 in the oxyanion hole, contrasting with the minimal interaction observed with SHS. These findings offer insights into the molecular mechanisms underlying surfactant-protein interactions, underscoring opportunities for engineering protein stability and functionality in the presence of surfactants.

Correlating Surface Activity with Interface-Induced Aggregation in a High-Concentration mAb Solution.

Interface-induced aggregation resulting in protein particle formation is an issue during the manufacturing and storage of protein-based therapeutics. High-concentration formulations of therapeutic proteins are even more prone to protein particle formation due to increased protein-protein interactions. However, the dependence of interface-induced protein particle formation on bulk protein concentration is not understood. Furthermore, the formation of protein particles is often mitigated by the addition of polysorbate-based surfactants. However, the details of surfactant-protein interactions that prevent protein particle formation at high concentrations remain unclear. In this work, a tensiometer technique was used to evaluate the surface pressure of an industrially relevant mAb at different bulk concentrations, and in the absence and presence of a polysorbate-based surfactant, polysorbate 20 (PS20). The adsorption kinetics was correlated with subvisible protein particle formation at the air-water interface and in the bulk protein solution using a microflow imaging technique. Our results showed that, in the absence of any surfactant, the number of subvisible particles in the bulk protein solutions increased linearly with mAb concentration, while the number of protein particles measured at the interface showed a logarithmic dependence on bulk protein concentration. In the presence of surfactants above the critical micelle concentration (CMC), our results for low-concentration mAb solutions (10 mg/mL) showed an interface that is surfactant-dominated, and particle characterization results showed that the addition of the surfactant led to reduced particle formation. In contrast, for the highest concentration (170 mg/mL), coadsorption of proteins and surfactants was observed at the air-water interface, even for surfactant formulations above CMC and the surfactant did not mitigate subvisible particle formation. Our results taken together provide evidence that the ratio between the surfactant and mAb molecules is an important consideration when formulating high-concentration mAb therapeutics to prevent unwanted aggregation.

Analysis of the Effects of Surfactants on Extracellular Polymeric Substances

Reservoirs after chemical flooding usually have residual chemicals, which can affect the driving effect of subsequent microbial drives. Among them, the effect of surfactants on the metabolites of oil-recovering bacteria is the most obvious. Therefore, this paper investigates the influence mechanism of sodium dodecyl sulfate (SDS) on the nature and structure of Extracellular Polymeric Substances (EPS) produced by metabolism of Enterobacter cloacae, through a variety of characterization to analysis the components and structure of EPS under SDS stress. The results showed that Enterobacter cloacae was identified as a glycolipid-producing strain, the main components of EPS were polysaccharides and proteins. The polysaccharide composition (%: w/w) was glucosamine, 37.2; glucose, 31.5; rhamnose, 26.3; xylose, 1.7; and unidentified sugar, 3.3; and the main component of proteins was polyglutamic acid. EPS under the stress of SDS showed an increase in the content of functional groups such as -C=O and -COOH and an increase in the cellular particle size, and production of EPS increased by 10.69 × 103 mg/L when the SDS concentration was 2.5 × 102 mg/L; 3D-EEM results showed that the components of all three types of EPS The 3D-EEM results showed that all three types of EPS fractions contained tryptophan and protein-like substances, humic acid-like substances were only distributed in the solubilized extracellular polymers (SL-EPS), and aromatic proteins were only present in the loosely bound type (LB-EPS) and tightly bound type (TB-EPS). In addition, the peaks representing humic-like substances showed a blue shift, indicating that SDS had the greatest effect on SL-EPS. This study provides a guidance for refining the mechanism of strain EPS response to reservoir residual surfactant SDS, and provides a more comprehensive and in-depth understanding of surfactant-protein interactions.

Insights into the Stabilization of Interferon Alpha by Two Surfactants Revealed by STD-NMR Spectroscopy

Surfactants are commonly used in biopharmaceutical formulations to stabilize proteins against aggregation. However, the choice of a suitable surfactant for a particular protein is decided mostly empirically, and their mechanism of action on molecular level is largely unknown. Here we show that a straightforward label-free method, saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy, can be used to detect protein-surfactant interactions in formulations of a model protein, interferon alpha. We find that polysorbate 20 binds with its fatty acid to interferon, and that the binding is stronger at pH closer to the isoelectric point of the protein. In contrast, we did not detect interactions between poloxamer 407 and interferon alpha. Neither of the two surfactants affected the tertiary structure and the thermal stability of the protein as evident from circular dichroism and nanoDSF measurements. Interestingly, both surfactants inhibited the formation of subvisible particles during long-term storage, but only polysorbate 20 reduced the amount of small soluble aggregates detected by size-exclusion chromatography. This proof-of-principle study demonstrates how STD-NMR can be employed to quickly assess surfactant-protein interactions and support the choice of surfactant in protein formulation.

Interaction between surfactants and proteins

Several approaches have been focused on the protein-surfactant interaction. Surfactant-protein interactions are very common in the fields of medicine, chemistry, biology etc. Indeed, many aspects of this interaction have been studied, such as the influence of the aggregation state of the surfactant (monomer, pre-micellar aggregate, micelle, and liposomes) on the protein structure, the properties of the surfactant-protein system, the characterization of the interaction sites on the protein surface, the identification of the intermediate protein conformations etc. The interaction of several types of proteins with the different kind of surfactant can furnish various information to the research of biochemical and biophysical systems, such as the structure-activity relationship of proteins as well as the mechanism of interaction between proteins and amphiphilic molecules. In this context, proteins with prosthetic group are very interesting ones, since the presence of the non-amino acid group can furnishes various information through different instrumental techniques of analysis, acting as a label of all polypeptide chains. The present work analyzes this topic and the potential of these studies.

Kinetic and thermodynamic of lactoferrin – Ethoxylated-nonionic surfactants supramolecular complex formation

Understanding nonionic surfactant-protein interactions is fundamental from both technological and scientific points of view. However, there is a complete absence of kinetic data for such interactions. We employed surface plasmon resonance (SPR) to determine the kinetic and thermodynamic parameters of bovine lactoferrin-Brij58 interactions at various temperatures under physiological conditions (pH 7.4). The adsorption process was accelerated with increasing temperature, while the desorption rate decreased, resulting in a more thermodynamically stable complex. The kinetic energetic parameters obtained for the formation of the activated complex, [bLF-Brij58]‡, indicated that the potential energy barrier for [bLF-Brij58]‡ formation arises primarily from the reduction in system entropy. [bLF-Brij58]○ formation was entropically driven, indicating that hydrophobic interactions play a fundamental role in bLF interactions with Brij58.

Interaction of a dirhamnolipid biosurfactant with sarcoplasmic reticulum calcium ATPase (SERCA1a)

The interaction of a dirhamnolipid biosurfactant secreted by Pseudomonas aeruginosa with calcium ATPase from sarcoplasmic reticulum (SR) was studied by means of different approaches, such as enzyme activity, fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and molecular docking simulations. The ATP hydrolysis activity was fully inhibited by incubation with dirhamnolipid (diRL) up to 0.1 mM concentration, corresponding to a surfactant concentration below membrane solubilization threshold. Surfactant-protein interaction induced conformational changes in the protein observed by an increase in the accessibility of tryptophan residues to the aqueous phase and by changes in the secondary structure of the protein as seen by fluorescence and FTIR spectroscopy. As a consequence, the protein become more unstable and denatured at lower temperatures, as seen by enzyme activity and DSC studies. Finally, these results were explained at molecular level throughout molecular docking simulations. It is concluded that there is a specific dirhamnolipid-protein interaction not related to the surface activity of the surfactant but to the particular physicochemical properties of the biosurfactant molecule.

Corn Oil-Water Separation: Interactions of Proteins and Surfactants at Corn Oil/Water Interfaces.

Purification and collection of industrial products from oil-water mixtures are commonly implemented processes. However, the efficiencies of such processes can be severely influenced by the presence of emulsifiers that induce the formation of small oil droplets dispersed in the mixtures. Understanding of this emulsifying effect and its counteractions which occur at the oil/water interface is therefore necessary for the improvement of designs of these processes. In this paper, we investigated the interfacial mechanisms of protein-induced emulsification and the opposing surfactant-induced demulsification related to corn oil refinement. At corn oil/water interfaces, the pH-dependent emulsifying function of zein protein, which is the major storage protein of corn, was elucidated by the surface/interface-sensitive sum frequency generation (SFG) vibrational spectroscopy technique. The effective stabilization of corn oil droplets by zein protein was illustrated and correlated to its ordered amide I group at the oil/water interface. Substantial decrease of this ordering with the addition of three industrial surfactants to corn oil-zein solution mixtures was also observed using SFG, which explains the surfactant-induced destabilization and coalescence of small oil droplets. Surfactant-protein interaction was then demonstrated to be the driving force for the disordering of interfacial proteins, either by disrupting protein layers or partially excluding protein molecules from the interface. The ordered zein proteins at the interface were therefore revealed to be the critical factor for the formation of corn oil-water emulsion.

Biophysical perspective of the binding of ester-functionalized gemini surfactants with catalase

Interaction of surfactants with biomacromolecules is an essential subject of biophysical chemistry to address their diverse applications in industry, biomedical, and cosmetic domains. In this context, we have examined the binding interactions of three ester-functionalized surfactants (m-E2-m) with bovine liver catalase (BLC, 10μM) by employing a multi-technique approach. The m-E2-m geminis quench fluorescence intensity of BLC through static procedure. The binding ability of concerned gemini surfactants was found to be in the order 12-E2-12 (Kb=2.3ÿ102)>16-E2-16 (Kb=1.1ÿ102)>14-E2-14 (Kb=1.0ÿ102). Quenching efficacy, as determined by Ksv values, were observed as 12-E2-12 (3.0ÿ102)>16-E2-16 (1.4ÿ102)>14-E2-14 (1.0ÿ102). The negative οG°b values (12-E2-12 (⿿13.48kJ/mol)>16-E2-16 (⿿11.65kJ/mol)>14-E2-14 (⿿11.41kJ/mol)) indicate spontaneous nature of m-E2-m⿿BLC interactions. UV⿿vis spectroscopy, circular dichroism (CD) and micropolarity (F1/F3) assessments indicate conformational changes in BLC upon m-E2-m combination. ITC confirms the stability of BLC upon gemini combination. Docking provides support to fluorescence results by presenting the localization site of m-E2-m surfactants near to aromatic residues (mainly Tyr, Trp and Phe). Moreover, since surfactant-protein interactions have essential miscellaneous implications, therefore, this study can be significant for industrial and biomedical realms.

When Enzymes and Green Surfactants Meet

Surfactants and proteins coexist in many different industries, ranging from detergents to pharmaceutics. Surfactant-protein interactions are multi-faceted and can range from limited interactions, as typically observed with nonionic surfactants, to complete denaturation of the protein, more typical of anionic surfactants such as sodium dodecyl sulphate (SDS). Denaturation of proteins and enzymes can be driven by both monomeric and micellar surfactant interactions [1].Biosurfactants are produced by microorganisms and have promising properties. They have strong interfacial properties [2] that are promising for industrial use. Despite growing interest, their impact on protein and enzyme stability remains at an early stage of investigation. Studies with model proteins suggest a relatively mild interaction with slow inactivation kinetics [3]. Membrane proteins can be refolded in their presence [4].Here we report interactions between industrial/detergent enzymes and two glycolipid-biosurfactants: Anionic rhamnolipid (RL) produced in Pseudomonas aeruginosa and mixed anionic/nonionic sophorolipid (SL) produced in Candida bombicola. RL and SL both act as mild biosurfactants that despite their anionic charge are compatible with industrial enzymes. The lipase from Thermomyces lanuginosus (TlL) shows pH dependent interactions. At pH 8 we do not detect interactions between TlL and RL or SL, with only minor perturbations to stability and activity. However, lowering pH from 8 to 6 favor stronger interactions between TlL and RL/SL that strongly stabilizes TlL and opens the active site with a 3- to 6-fold boost to activity. We use SAXS to qualitatively determine formation of complexes between TlL and SL and RL micelles at pH 6.1.Otzen, D.E., P. Sehgal, and P. Westh. J Colloid Interface Sci, 2009.329(2): p.273-83.2.Nguyen, T.T. and D.A. Sabatini. Int J Mol Sci, 2011.12(2): p.1232-44.3.Andersen, K.K. and D.E. Otzen. Biochim Biophys Acta, 2014.1844: p.2338-2345.4.Andersen, K.K. and D.E. Otzen. FEBS Lett, 2014.588: p.1955-60.

Binding of a novel 12-E2-12 gemini surfactant to xanthine oxidase: Analysis involving tensiometric, spectroscopic, microscopic and molecular docking approach

Binding interaction of a synthesized biodegradable gemini surfactant, ethane-1, 2-diyl bis(N, N-dimethyl-N-dodecylammoniumacetoxy) dichloride (12-E2-12), with bovine milk xanthine oxidase (XO) was studied using tensiometry, fluorescence spectroscopy, UV, CD, FT-IR, TEM and molecular docking. Tensiometry revealed lowering in surface tension (γ) and critical micelle concentration (CMC) of 12-E2-12 upon XO combination, suggesting a significant interaction between XO and 12-E2-12 (both in the bulk as well as at interface). Intrinsic fluorescence studies depict that 12-E2-12 quenches XO fluorescence intensity through static mechanism. The magnitude of binding parameters infers substantial and effective binding of 12-E2-12 to (XO). ANS and pyrene fluorescence demonstrate the exposure of aromatic residues (tyrosine/tryptophan) to a non-polar environment. UV, circular dichroism (CD) and FT-IR results delineate change in the secondary structure of the enzyme XO. Microscopic TEM micrographs confirm the disrupture of enzyme structure at higher concentrations of 12-E2-12. Molecular docking results show that 12-E2-12 binds to XO in the vicinity of both hydrophobic and hydrophilic residues, inferring that binding is governed by both hydrophilic and hydrophobic forces. This study may be of significance in biomedical world to further interpret mechanistic treatment modes of diseases like gout and hyperuricemia. Moreover, this study provides deeper biophysical insight into surfactant–protein interactions.

In silico Design and Analysis of G. Moniliformis Class II Hydrophobin Inhibitor as a Potential Antifungal Drug

Gibberella moniliformis (anamorph: Fusarium verticillioides) is a fungal pathogen destructive to over 11,000 plant species. It is known to cause severe grain loss in maize and rice, as well as carcinogenic diseases in both humans and animals upon ingestion of the infested grains. Such a significant economic impact of G. moniliformis can be credited to class II hydrophobins generally secreted and localized on the outer surface of conidia and of the hyphal wall. These small related surface-active proteins (+/- 100 amino acids long and 10 kDa weight) can self assemble at hydrophilic: hydrophobic interfaces into different forms of nanometric biofilms about 10nm wide. Based on this unique property, class II hydrophobins are involved in signalling and attachment of aerial structures (like mycelia, hyphae, and spores) to hydrophobic surfaces of host plant during fungal pathogenesis. This paper thus seeks to comparatively model the 3D structure of class II hydrophobins, to computationally determine their surfactant-protein interactions ability to a potential inhibitor using molecular docking techniques, and to statistically predict the ADME-T properties of the lead molecule.

Amino acid-based cationic gemini surfactant–protein interactions

A novel cationic amino acid-based gemini surfactant derived from cysteine, (C12Cys)2, has been synthesized and both its supramolecular behaviour and its interaction with the model protein bovine serum albumin (BSA) have been characterized under physiological mimetic conditions (PBS, pH 7.4). Surface tension measurements were used to obtain important system parameters, such as critical micelle concentration (CMC), critical aggregation concentration (CAC), protein saturation point (PSP), maximum surface excess concentration (Γmax), minimum surface area per molecule (Amin) at the air/solution interface and the degree of surfactant binding to protein (α). Formation of a protein–surfactant complex was confirmed by UV–vis and fluorescence spectroscopy. Fluorescence quenching measurements allowed determination of the Stern–Volmer quenching constant (KSV), surfactant–protein binding constant (Ka) and number of binding sites (n). UV–vis measurements and the calculated value for the bimolecular quenching constant (kq) suggest that (C12Cys)2 quenches BSA intrinsic fluorescence by a static quenching mechanism.

Drug–protein interactions in micellar media: Thermodynamic aspects

Devising directions for surfactant assisted effective controlled release of drugs requires a quantitative and qualitative understanding of the drug–protein, drug–surfactant, and surfactant–protein interactions. In this work, the effect of micellar environment on the binding of naproxen and diclofenac sodium with bovine serum albumin has been studied. The isothermal titration calorimetric (ITC) results suggest that the binding of naproxen is reduced with the protein when it is delivered from micellar media. However, the binding is observed to be strengthened for diclofenac sodium. The differential scanning calorimetric results suggest that the integrity of the binding sites is not altered under the employed micellar conditions. The ITC results further suggest that the numbers of naproxen and diclofenac sodium molecules partitioning/binding per micelle of HTAB are 15 and 38, respectively. In the micelles, naproxen is restricted to the surface of the micelles whereas diclofenac sodium is able to partition in the palisade layers. A detailed understanding of the energetics of the drug–protein interactions under different conditions helps in devising directions for effective drug delivery. The ITC and DSC results have shown that the micelles assisted drug–protein interactions are modified depending on the hydrophobic content of the drug.

ChemInform Abstract: Thermodynamics and Binding Properties of Surfactant—Protein Interactions

AbstractReview: 125 refs.

Adsorption of antibody onto Pluronic F68-covered nanoparticles: link with surface properties

The use of nanoparticles as drug delivery systems is an emerging application to improve intravenous therapy. Controlling the biocompatibility of the nanoparticles is a crucial step towards the optimal implementation of these systems. Adsorption of serum components onto the nanoparticles is driven mainly by hydrophobic forces. Thus, incorporation of hydrophilic polymers such as polyethylene oxide (PEO) derivatives to the nanostructure surface reduces the interaction of nanoparticles with blood stream components (IgG). The effectiveness of the poloxamer for reducing protein adsorption depends on the resistance of this coating layer. A fundamental understanding of the properties of this surface coating is crucial towards the rational design of these systems. Here, we have used an innovative combination of experimental techniques to evaluate the properties of the nanoparticles and more specifically, the mechanical properties of the coating. Electrophoretic mobility and colloidal stability data suggest similar surface characteristics between IgG–Pluronic–polystyrene (PS) and IgG–PS complexes, indicating that the protein adsorption is just slightly reduced by the presence of poloxamer. Nevertheless, the biological activity of the adhered antibodies suggests that the Pluronic F68 significantly altered their immunoactivity. The decrease in the activity might indicate a partial denaturation of the protein and/or changes in the preferential orientation when adsorbing caused by the surfactant–protein interactions. The surface characterisation of the IgG layers adsorbed onto a Pluronic covered surface importantly provides evidence of the conformational change undergone by the protein, supporting the partial protein denaturation suggested by the loss of immunoreactivity in the IgG–Pluronic–PS particles. The use of surface tension to obtain structural and mechanical information about the coating procedure is a novel approach to understand generic features of the biocompatibility of colloidal systems. These results may help to understand why drug nanocarriers coated by poloxamers improve their long-circulating properties in comparison with uncoated particles.

Surfactant cleaning of ultrafiltration membranes fouled by whey

A polyethersulphone ultrafiltration membrane was prepared for concentration of whey. The membrane was fouled by whey and the effect of different cleaning agents on flux recovery of the fouled membrane was studied. The optimum cleaning procedure for membrane regeneration was elucidated. The results showed that a combination of surfactants (anionic, cationic and nonionic) may be employed as the optimum cleaning agent for maximum flux recovery. The fluorescence studies revealed that the cationic surfactant interact with proteins by breaking the intra‐chain hydrophobic bonding and providing electrostatic repulsion. Changing the alkyl chain from dodecyl to hexadecyl increases the interaction of surfactant–protein. Dodecyltrimethylammonium bromide (DTAB) provided a weak interaction with whey proteins than to tetradecyltrimethylammonium bromide (TTAB) and cetyltrimethylammonium bromide (CTAB). All data obtained in this study support a surfactant–protein interaction in which hydrophobic forces play a dominant role. The nonionic surfactants poly(oxyethylene) isooctyl phenyl ether (TX‐100) and anionic surfactants SDS interact with amino acids in the inner protein structure thus denaturate tertiary protein structure and reduce hydrophobic interaction of proteins by membrane surface.

Interaction of Surfactant Protein A with the Intermediate Filaments Desmin and Vimentin

Surfactant protein A (SP-A), a member of the collectin family that modulates innate immunity, has recently been involved in the physiology of reproduction. Consistent with the activation of ERK-1/2 and COX-2 induced by SP-A in myometrial cells, we reported previously the presence of two major proteins recognized by SP-A in these cells. Here we identify by mass spectrometry one of these SP-A targets as the intermediate filament (IF) desmin. In myometrial preparations derived from desmin-deficient mice, the absence of binding of SP-A to any 50 kDa protein confirmed the identity of this SP-A-binding site as desmin. Our data based on partial chymotrypsin digestion of pure desmin suggested that SP-A recognizes especially its rod domain, which is known to play an important role during the assembly of desmin into filaments. In line with that, electron microscopy experiments showed that SP-A inhibits in vitro the polymerization of desmin filaments. SP-A also recognized in vitro polymerized filaments in a calcium-dependent manner at a physiological ionic strength but not the C1q receptor gC1qR. Furthermore, Texas Red-labeled SP-A colocalized with desmin filaments in myometrial cells. Interestingly, vimentin, the IF characteristic of leukocytes, is one of the major proteins recognized by SP-A in protein extracts of U937 cells after PMA-induced differentiation of this monocytic cell line. Interaction of SP-A with vimentin was further confirmed using recombinant vimentin in solid-phase binding assays. The ability of SP-A to interact with desmin and vimentin, and to prevent polymerization of desmin monomers, shed light on unexpected and wider biological roles of this collectin.

Protein–surfactant interaction: Differences between fluorinated and hydrogenated surfactants

The interactions of proteins with fluorinated/hydrogenated surfactants were investigated by circular dichroism and turbidity measurement. Pairs of fluorinated and hydrogenated surfactants with similar critical micelle concentrations (cmc), including sodium perfluorooctanoate/sodium decylsulfate and lithium perfluorononanoate/sodium dodecylsulfate were compared in view of their interactions with proteins including BSA, lysozyme, β-lactoglobulin and ubiquitin. It was found that fluorinated surfactants exhibited stronger interactions with proteins than hydrogenated ones, which, however, depended on the structures of both proteins and surfactant molecules. If the proteins are very stable, or the surfactant–protein interactions are very strong, such differences between the two kinds of surfactants might be indistinguishable.

Direct Interaction of Surfactant Protein A with Myometrial Binding Sites: Signaling and Modulation by Bacterial Lipopolysaccharide1

Surfactant protein A (SFTPA1), a member of the collagenous lectin (collectin) family, was first described as a major constituent of lung surfactant, but has recently also been found in the female genital tract. Various microorganisms colonize this area and may cause intrauterine infection or trigger preterm labor. We found that SFTPA1 was not produced in the uterus. Instead, it was immunodetected transiently in rat myometrium at the end (Days 19 and 21) of gestation, but not postpartum, and in cultured myometrial cells. Fluorescence microscopy showed that Texas Red-labeled SFTPA1 bound to myometrial cells. This result was confirmed by biochemical approaches. [(125)I]-SFTPA1 bound to two myometrial cell proteins (55 and 210 kDa). This interaction was dependent on the integrity of the collagenlike domain of SFTPA1. SFTPA1 rapidly activated mitogen-activated protein kinase 1/3 (MAPK1/3) in myometrial cells. Bacterial lipopolysaccharide (LPS), an agent known to trigger uterine contractions and preterm birth, also activated MAPK1/3. The prolonged treatment of myometrial cells with LPS or SFTPA1 upregulated PTGS2 (COX2) protein levels. The addition of rough-type LPS to SFTPA1 blocked the interaction of SFTPA1 with its binding sites and the activation of MAPK1/3 and PTGS2 by SFTPA1. Our data provide the first demonstration of a direct effect of SFTPA1 on rat myometrial cells and inhibitory cross talk between SFTPA1 and LPS signals, providing new insight into the mechanisms of normal and preterm parturition.