Molecular Characteristics and Biological Functions of Surface-Active and Surfactant Proteins.

Many critical biological processes take place at hydrophobic:hydrophilic interfaces, and a wide range of organisms produce surface-active proteins and peptides that reduce surface and interfacial tension and mediate growth and development at these boundaries. Microorganisms produce both small lipid-associated peptides and amphipathic proteins that allow growth across water:air boundaries, attachment to surfaces, predation, and improved bioavailability of hydrophobic substrates. Higher-order organisms produce surface-active proteins with a wide variety of functions, including the provision of protective foam environments for vulnerable reproductive stages, evaporative cooling, and gas exchange across airway membranes. In general, the biological functions supported by these diverse polypeptides require them to have an amphipathic nature, and this is achieved by a diverse range of molecular structures, with some proteins undergoing significant conformational change or intermolecular association to generate the structures that are surface active.

Segregation of co-cultured multicellular systems: review and modeling consideration.

Cell segregation caused by collective cell migration (CCM) is crucial for morphogenesis, functional development of tissue parts, and is an important aspect in other diseases such as cancer and its metastasis process. Efficiency of the cell segregation depends on the interplay between: (1) biochemical processes such as cell signaling and gene expression and (2) physical interactions between cells. Despite extensive research devoted to study the segregation of various co-cultured systems, we still do not understand the role of physical interactions in cell segregation. Cumulative effects of these physical interactions appear in the form of physical parameters such as: (1) tissue surface tension, (2) viscoelasticity caused by CCM, and (3) solid stress accumulated in multicellular systems. These parameters primarily depend on the interplay between the state of cell-cell adhesion contacts and cell contractility. The role of these physical parameters on the segregation efficiency is discussed on model systems such as co-cultured breast cell spheroids consisting of two subpopulations that are in contact. This review study aims to: (1) summarize biological aspects related to cell segregation, mechanical properties of cell collectives, effects along the biointerface between cell subpopulations and (2) describe from a biophysical/mathematical perspective the same biological aspects summarized before. So that overall it can illustrate the complexity of the biological systems that translate into very complex biophysical/mathematical equations. Moreover, by presenting in parallel these two seemingly different parts (biology vs. equations), this review aims to emphasize the need for experiments to estimate the variety of parameters entering the resulting complex biophysical/mathematical models.

Surface tension of cavitation bubbles.

We have studied homogeneous cavitation in liquid nitrogen and normal liquid helium. We monitor the fluid content in a large number of independent mesopores with an ink-bottle shape, either when the fluid in the pores is quenched to a constant pressure or submitted to a pressure decreasing at a controlled rate. For both fluids, we show that, close enough to their critical point, the cavitation pressure threshold is in good agreement with the Classical Nucleation Theory (CNT). In contrast, at lower temperatures, deviations are observed, consistent with a reduction of the surface tension for bubbles smaller than two nanometers in radius. For nitrogen, we could accurately measure the nucleation rate as a function of the liquid pressure down to the triple point, where the critical bubble radius is about one nanometer. We find that CNT still holds, provided that the curvature dependence of the surface tension is taken into account. Furthermore, we evaluate the first- and second-order corrections in curvature, which are in reasonable agreement with recent calculations for a Lennard-Jones fluid.

Proximity to criticality predicts surface properties of biomolecular condensates.

It has recently become appreciated that cells self-organize their interiors through the formation of biomolecular condensates. These condensates, typically formed through liquid-liquid phase separation of proteins, nucleic acids, and other biopolymers, exhibit reversible assembly/disassembly in response to changing conditions. Condensates play many functional roles, aiding in biochemical reactions, signal transduction, and sequestration of certain components. Ultimately, these functions depend on the physical properties of condensates, which are encoded in the microscopic features of the constituent biomolecules. In general, the mapping from microscopic features to macroscopic properties is complex, but it is known that near a critical point, macroscopic properties follow power laws with only a small number of parameters, making it easier to identify underlying principles. How far does this critical region extend for biomolecular condensates and what principles govern condensate properties in the critical regime? Using coarse-grained molecular-dynamics simulations of a representative class of biomolecular condensates, we found that the critical regime can be wide enough to cover the full physiological range of temperatures. Within this critical regime, we identified that polymer sequence influences surface tension predominately via shifting the critical temperature. Finally, we show that condensate surface tension over a wide range of temperatures can be calculated from the critical temperature and a single measurement of the interface width.

The rearrangement of co-cultured cellular model systems via collective cell migration.

Cancer invasion through the surrounding epithelium and extracellular matrix (ECM) is the one of the main characteristics of cancer progression. While significant effort has been made to predict cancer cells response under various drug therapies, much less attention has been paid to understand the physical interactions between cancer cells and their microenvironment, which are essential for cancer invasion. Considering these physical interactions on various co-cultured in vitro model systems by emphasizing the role of viscoelasticity, the tissue surface tension, solid stress, and their inter-relations is a prerequisite for establishing the main factors that influence cancer cell spread and develop an efficient strategy to suppress it. This review focuses on the role of viscoelasticity caused by collective cell migration (CCM) in the context of mono-cultured and co-cultured cancer systems, and on the modeling approaches aimed at reproducing and understanding these biological systems. In this context, we do not only review previously-published biophysics models for collective cell migration, but also propose new extensions of those models to include solid stress accumulated within the spheroid core region and cell residual stress accumulation caused by CCM.

The dynamics along the biointerface between the epithelial and cancer mesenchymal cells: Modeling consideration.

Epithelial cancer is the one of most lethal cancer type worldwide. Targeting the early stage of disease would allow dramatic improvements in the survival of cancer patients. The early stage of the disease is related to cancer cell spreading across surrounding healthy epithelium. Consequently, deeper insight into cell dynamics along the biointerface between epithelial and cancer (mesenchymal) cells is necessary in order to control the disease as soon as possible. Cell dynamics along this epithelial-cancer biointerface is the result of the interplay between various biological and physical mechanisms. Despite extensive research devoted to study cancer cell spreading across the epithelium, we still do not understand the physical mechanisms which influences the dynamics along the biointerface. These physical mechanisms are related to the interplay between physical parameters such as: (1) interfacial tension between cancer and epithelial subpopulations, (2) established interfacial tension gradients, (3) the bending rigidity of the biointerface and its impact on the interfacial tension, (4) surface tension of the subpopulations, (5) viscoelasticity caused by collective cell migration, and (6) cell residual stress accumulation. The main goal of this study is to review some of these physical parameters in the context of the epithelial/cancer biointerface elaborated on the model system such as the biointerface between breast epithelial MCF-10A cells and cancer MDA-MB-231 cells and then to incorporate these parameters into a new biophysical model that could describe the dynamics of the biointerface. We conclude by discussing three biophysical scenarios for cell dynamics along the biointerface, which can occur depending on the magnitude of the generated shear stress: a smooth biointerface, a slightly-perturbed biointerface and an intensively-perturbed biointerface in the context of the Kelvin-Helmholtz instability. These scenarios are related to the probability of cancer invasion.

Mechanical Tester Driven by Surface Tension.

The measurement of in-plane mechanical properties, such as Young's modulus and strength, of thin and stretchable materials has long been a challenge. Existing measurements, including wrinkle instability and nano indentation, are either indirect or destructive, and are inapplicable to meshes or porous materials, while the conventional tension test fails to measure the mechanical properties of nanoscale films. Here, we report a technique to test thin and stretchable films by loading a thin film afloat via differential surface tension and recording its deformation. We have demonstrated the method by measuring the Young's moduli of homogeneous films of soft materials including polydimethylsiloxane and Ecoflex and verified the results with known values. We further measured the strain distributions of meshes, both isotropic and anisotropic, which were otherwise nearly impossible to measure. The method proposed herein is expected to be generally applicable to many material systems that are thin, stretchable, and water-insoluble.

Comparative Biophysical Study of Clinical Surfactants using Constrained Drop Surfactometry.

Surfactant replacement therapy is crucial in managing neonatal respiratory distress syndrome (RDS). Currently licensed clinical surfactants in the United States and Europe, including Survanta, Infasurf, Curosurf, and Alveofact, are all derived from bovine or porcine sources. We conducted a comprehensive examination of the biophysical properties of these four clinical surfactant preparations under physiologically relevant conditions, utilizing constrained drop surfactometry (CDS). The assessed biophysical properties included the adsorption rate, quasi-static and dynamic surface activity, resistance to surfactant inhibition by meconium, and the morphology of the adsorbed surfactant films. This comparative study unveiled distinct in vitro biophysical properties of these clinical surfactants and revealed correlations between their chemical composition, lateral film structure, and biophysical functionality. Notably, at 1 mg/mL, Survanta exhibited a significantly lower adsorption rate compared to the other preparations at the same surfactant concentration. At 10 mg/mL, Infasurf, Curosurf, and Survanta all demonstrated excellent dynamic surface activity, while Alveofact exhibited the poorest quasi-static and dynamic surface activity. The suboptimal surface activity of Alveofact is found to be correlated with its unique monolayer-predominant morphology, in contrast to other surfactants forming multilayers. Curosurf, in particular, showcased superior resistance to biophysical inhibition by meconium compared to other preparations. Understanding the diverse biophysical behaviors of clinical surfactants provides crucial insights for precision and personalized design in treating RDS and other respiratory conditions. The findings from this study contribute valuable perspectives for development of more efficacious and fully synthetic surfactant preparations.

Capillarity and active cell movement at mesendoderm translocation in the Xenopus gastrula.

During Xenopus gastrulation, leading edge mesendoderm (LEM) advances animally as a wedge-shaped cell mass over the vegetally moving blastocoel roof (BCR). We show that close contact across the BCR-LEM interface correlates with attenuated net advance of the LEM, which is pulled forward by tip cells while the remaining LEM frequently separates from the BCR. Nevertheless, lamellipodia persist on the detached LEM surface. They attach to adjacent LEM cells and depend on PDGF-A, cell-surface fibronectin and cadherin. We argue that active cell motility on the LEM surface prevents adverse capillary effects in the liquid LEM tissue as it moves by being pulled. It counters tissue surface-tension effects with oriented cell movement and bulges the LEM surface out to keep it close to the curved BCR without attaching to it. Proximity to the BCR is necessary, in turn, for the maintenance and orientation of lamellipodia that permit mass cell movement with minimal substratum contact. Together with a similar process in epithelial invagination, vertical telescoping, the cell movement at the LEM surface defines a novel type of cell rearrangement: vertical shearing.

An experimental and modeling approach to describe the deactivation of cellulases at the air-liquid interface.

Understanding the reaction mechanisms involved in the enzymatic hydrolysis of cellulose is important because it is kinetically the most limiting step of the bioethanol production process. The present work focuses on the enzymatic deactivation at the air-liquid interface, which is one of the aspects contributing to this global deactivation. This phenomenon has already been experimentally proven, but this is the first time that a model has been proposed to describe it. Experiments were performed by incubating Celluclast cocktail solutions on an orbital stirring system at different enzyme concentrations and different surface-to-volume ratios. A 5-day follow-up was carried out by measuring the global FPase activity of cellulases for each condition tested. The activity loss was proven to depend on both the air-liquid surface area and the enzyme concentration. Both observations suggest that the loss of activity takes place at the air-liquid surface, the total amount of enzymes varying with volume or enzyme concentration. Furthermore, tests performed using five individual enzymes purified from a Trichoderma reesei cocktail showed that the only cellulase that is deactivated at the air-liquid interface is cellobiohydrolase II. From the experimental data collected by varying the initial enzyme concentration and the ratio surface to volume, it was possible to develop, for the first time, a model that describes the loss of activity at the air-liquid interface for this configuration.

Development of Cholinium-Based API Ionic Liquids with Enhanced Drug Solubility: Biological Evaluation and Interfacial Properties.

We report an efficient sustainable two-step anion exchange synthetic procedure for the preparation of choline API ionic liquids (Cho-API-ILs) that contain active pharmaceutical ingredients (APIs) as anions combined with choline-based cations. We have evaluated the in vitro cytotoxicity for the synthesized compounds using three different cells lines, namely, HEK293 (normal kidney cell line), SW480, and HCT 116 (colon carcinoma cells). The solubility of APIs and Cho-API-ILs was evaluated in water/buffer solutions and was found higher for Cho-API-ILs. Further, we have investigated the antimicrobial potential of the pure APIs, ILs, and Cho-API-ILs against clinically relevant microorganisms, and the results demonstrated the promise of Cho-API-ILs as potent antimicrobial agents to treat bacterial infections. Moreover, the aggregation and adsorption properties of the Cho-API-ILs were observed by using a surface tension technique. The aggregation behavior of these Cho-API-ILs was further supported by conductivity and pyrene probe fluorescence. The thermodynamics of aggregation for Cho-API-ILs has been assessed from the temperature dependence of surface tension. The micellar size and their stability have been studied by dynamic light scattering, transmission electron microscopy, and zeta potential. Therefore, the duality in the nature of Cho-API-ILs has been explored with the upgradation of their physical, chemical, and biopharmaceutical properties, which enhance the opportunities for advances in pharmaceutical sciences.

Mechanistic Insights into the Adsorption of Monoclonal Antibodies at the Water/Vapor Interface.

Monoclonal antibodies (mAbs) are active components of therapeutic formulations that interact with the water-vapor interface during manufacturing, storage, and administration. Surface adsorption has been demonstrated to mediate antibody aggregation, which leads to a loss of therapeutic efficacy. Controlling mAb adsorption at interfaces requires a deep understanding of the microscopic processes that lead to adsorption and identification of the protein regions that drive mAb surface activity. Here, we report all-atom molecular dynamics (MD) simulations of the adsorption behavior of a full IgG1-type antibody at the water/vapor interface. We demonstrate that small local changes in the protein structure play a crucial role in promoting adsorption. Also, interfacial adsorption triggers structural changes in the antibody, potentially contributing to the further enhancement of surface activity. Moreover, we identify key amino acid sequences that determine the adsorption of antibodies at the water-air interface and outline strategies to control the surface activity of these important therapeutic proteins.

Comparative Study of Latanoprost Drug Delivery Systems for Glaucoma Treatment and Their Interaction with the Tear Film Lipid Layer Models.

This study investigates the interaction of two approved and one newly developed latanoprost formulation with in vitro and in silico models of the tear film and tear film lipid layer (TFLL). Latanoprost, a prostaglandin analogue used for intraocular elevated pressure treatment, is topically delivered by nanocarriers within aqueous solutions or emulsions. The study focuses on the impact of these carriers on drug interactions with the tear film and their effect on the TFLL. Three different types of latanoprost carriers, micellar, nanoemulsion, and polymer-based, were compared, and each revealed distinct interaction patterns with the TFLL. Surface pressure kinetics demonstrated a rapid increase for the benzalkonium chloride formulation and a slow rise for the preservative-free variants. Visualization of the acellular in vitro TFLL model revealed different patterns of incorporation for each formulation, indicating unique interaction mechanisms. Molecular dynamics simulations further revealed different mechanisms of drug release in the TFLL between micellar and nanoemulsion formulations. In-depth examination highlighted the role of triglyceride molecules in replenishing the nonpolar layer of the TFLL, which suggests potential improvements in ocular surface compatibility by adjusting the quality and concentration of the oily phase. These findings suggest the potential for optimizing latanoprost formulations by tuning the oily phase-to-surfactant ratio and selecting suitable surfactants.

Evidence of Surface-Tension Lowering of Atmospheric Aerosols by Organics from Field Observations in an Urban Atmosphere: Relation to Particle Size and Chemical Composition.

Surface-active organics lower the aerosol surface tension (σs/a), leading to enhanced cloud condensation nuclei (CCN) activity and potentially exerting impacts on the climate. Quantification of σs/a is mainly limited to laboratory or modeling work for particles with selected sizes and known chemical compositions. Inferred values from ambient aerosol populations are deficient. In this study, we propose a new method to derive σs/a by combining field measurements made at an urban site in northern China with the κ-Köhler theory. The results present new evidence that organics remarkably lower the surface tension of aerosols in a polluted atmosphere. Particles sized around 40 nm have an averaged σs/a of 53.8 mN m-1, while particles sized up to 100 nm show σs/a values approaching that of pure water. The dependence curve of σs/a with the organic mass resembles the behavior of dicarboxylic acids, suggesting their critical role in reducing the surface tension. The study further reveals that neglecting the σs/a lowering effect would result in lowered ultrafine CCN (diameter <100 nm) concentrations by 6.8-42.1% at a typical range of supersaturations in clouds, demonstrating the significant impact of surface tension on the CCN concentrations of urban aerosols.

Polyhedral Vinyl Polymer Particles Synthesized Via Solvent-Free Radical Polymerization.

Liquid marbles (LMs) with a cubic shape are created by using various vinyl monomers as an inner liquid and polymer plates with mm size as a stabilizer. The relationship between the surface tension of the vinyl monomers and formability of the LMs is investigated. LMs can be fabricated using vinyl monomers with surface tensions of 42.7-40.3 mN m-1. The cubic polymer particles are successively synthesized via free-radical polymerizations by irradiation of the cubic LMs with UV light in a solvent-free manner. In addition, controlling the number of polymer plates per one LM, the shape of the plate or the coalescence of the LMs can lead to production of polymer particles with desired forms (e.g., Platonic and rectangular solids) that correspond to the shapes of the original LMs.

Evaluating Novel SP-B and SP-C Synthetic Analogues for Pulmonary Surfactant Efficacy.

Pulmonary surfactants, a complex assembly of phospholipids and surfactant proteins such as SP-B and SP-C, are critical for maintaining respiratory system functionality by lowering surface tension (ST) and preventing alveolar collapse. Our study introduced five synthetic SP-B peptides and one SP-C peptide, leading to the synthesis of CHAsurf candidates (CHAsurf-1 to CHAsurf-5) for evaluation. We utilized a modified Wilhelmy balance test to assess the surface tension properties of the surfactants, measuring spreading rate, surface adsorption, and ST-area diagrams to comprehensively evaluate their performance. Animal experiments were performed on New Zealand white rabbits to test the efficacy of CHAsurf-4B, a variant chosen for its economic viability and promising ST reduction properties, comparable to Curosurf®. The study confirmed that higher doses of SP-B in CHAsurf-4 are associated with improved ST reduction. However, due to cost constraints, CHAsurf-4B was selected for in vivo assessment. The animal model revealed that CHAsurf-4B could restore alveolar structure and improve lung elasticity, akin to Curosurf®. Our research highlights the significance of cysteine residues and disulfide bonds in the structural integrity and function of synthetic SP-B analogues, offering a foundation for future surfactant therapy in respiratory disorders. This study's findings support the potential of CHAsurf-4B as a therapeutic agent, meriting further investigation to solidify its role in clinical applications.

Superelastic oxide micropillars enabled by surface tension-modulated 90° domain switching with excellent fatigue resistance.

Superelastic materials capable of recovering large nonlinear strains are ideal for a variety of applications in morphing structures, reconfigurable systems, and robots. However, making oxide materials superelastic has been a long-standing challenge due to their intrinsic brittleness. Here, we fabricate ferroelectric BaTiO3 (BTO) micropillars that not only are superelastic but also possess excellent fatigue resistance, lasting over 1 million cycles without accumulating residual strains or noticeable variation in stress-strain curves. Phase field simulations reveal that the large recoverable strains of BTO micropillars arise from surface tension-modulated 90° domain switching and thus are size dependent, while the small energy barrier and ultralow energy dissipation are responsible for their unprecedented cyclic stability among superelastic materials. This work demonstrates a general strategy to realize superelastic and fatigue-resistant domain switching in ferroelectric oxides for many potential applications.

Microscopic origin of the effect of substrate metallicity on interfacial free energies.

We investigate the effect of the metallic character of solid substrates on solid-liquid interfacial thermodynamics using molecular simulations. Building on the recent development of a semiclassical Thomas-Fermi model to tune the metallicity in classical molecular dynamics simulations, we introduce a thermodynamic integration framework to compute the evolution of the interfacial free energy as a function of the Thomas-Fermi screening length. We validate this approach against analytical results for empty capacitors and by comparing the predictions in the presence of an electrolyte with values determined from the contact angle of droplets on the surface. The general expression derived in this work highlights the role of the charge distribution within the metal. We further propose a simple model to interpret the evolution of the interfacial free energy with voltage and Thomas-Fermi length, which allows us to identify the charge correlations within the metal as the microscopic origin of the evolution of the interfacial free energy with the metallic character of the substrate. This methodology opens the door to the molecular-scale study of the effect of the metallic character of the substrate on confinement-induced transitions in ionic systems, as reported in recent atomic force microscopy and surface force apparatus experiments.

Thermodynamics of interfaces extended to nanoscales by introducing integral and differential surface tensions.

As a system shrinks down in size, more and more molecules are found in its surface region, so surface contribution becomes a large or even a dominant part of its thermodynamic potentials. Surface tension is a venerable scientific concept; Gibbs defined it as the excess of grand potential of an inhomogeneous system with respect to its bulk value per interface area [J. W. Gibbs, "The Collected Works" in Thermodynamics (1928), Vol. 1]. The mechanical definition expresses it in terms of pressure tensor. So far, it has been believed the two definitions always give the same result. We show that the equivalence can break down for fluids confined in narrow pores. New concepts of integral and differential surface tensions, along with integral and differential adsorptions, need to be introduced for extending Gibbs thermodynamics of interfaces. We derived two generalized Gibbs adsorption equations. These concepts are indispensable for an adequate description of nanoscale systems. We also find a relation between integral surface tension and Derjaguin's disjoining pressure. This lays down the basis for measuring integral and differential surface tensions from disjoining pressure by using an atomic force microscope.

Sustainable trehalose lipid production by Rhodotorula sp.: a promising bio-based alternative.

Global environmental concerns drive research toward the development of new eco-friendly compounds to replace pollutant chemicals. This study focuses on optimizing the production of trehalose lipids (TLs), which are glycolipid biosurfactants (BS) with various applications like antimicrobial or surface tension reduction. New microorganism sources, growth conditions, medium composition, purification conditions, and physicochemical properties of TLs are studied. Addressing a microscale approach, TLs production was successfully achieved using Rhodotorula sp. and Rhodococcus erythropolis to compare, with different media compositions including glucose-based and salt media supplemented with glycerol, glucose, n-hexadecane, n-dodecane. Liquid-liquid extraction using ethyl acetate and methanol was employed for compound extraction, followed by characterization using analytical methods such as Thin layer chromatography (TLC), High performance liquid chromatography (HPLC), and UHPLC. The produced TLs exhibited a minimum surface tension of 47 mN/m and a critical micellar concentration of 4.4 mg/mL. This study also identified Rhodotorula sp. as a new sustainable producer of TLs with improved productivity.