Ectoin®: A Cell-Protecting Molecule from Extreme Environments!
What is Ectoin®?
Ectoin® is a low molecular, cyclic amino acid derivative, which is produced by many different extremophilic microorganisms. Ectoin® belongs to the class of compatible solutes also called extremolytes (osmolytes from extremophiles) and was first isolated by Galinski and colleagues from the bacterium Ectothiorhodospira halo- chloris found in Wadi Natrun, Egypt.
In extremophilic microorganisms these low molecular weight compounds are ac- cumulated in response to increased extracellular salt concentrations, but also as a response to other environmental changes, e.g. increased temperature. This is one of the ingenious strategies these organisms have developed to cope with harsh environmental conditions.
Extremolytes minimise the denaturation of biopolymers that usually occurs under conditions of water stress and are compatible with the intracellular machinery at high (>1M) concentrations. Extremolytes have a wide range of applications due to their protection of biological macromolecules and cells from damage by external stresses.
Ectoin® Comes from Extreme Environments, Protecting Microbial Survival
Extremophiles are a group of microorganisms that thrive in extreme environments, such as extreme cold, heat, acidity, alkalinity, salinity, and high pressure. Such bacteria often develop unique physiological characteristics to adapt and cope with these extreme conditions.
How extremophiles survive in extreme environments relies heavily on their unique cell structures. Thermophiles are the most common group of extremophiles, and the cell membrane, which is vital for maintaining cell integrity and growth, exhibits different lipid compositions compared to normal bacteria in high-temperature bacteria.
The Asia-Pacific Rim volcanic belt has many geothermal hot spring areas on islands, including submarine hydrothermal vents, alkaline or acidic geothermal spring areas, and other extreme environments. Previous studies have revealed the existence of numerous high-temperature microorganisms in these natural hot environments.
Ectoin®, an extremolyte molecule, protects extremophiles. Derived from an original strain discovered on the Bonaire salt flats in the Caribbean by the German pharmaceutical company Bitop AG, this molecule is produced using patented biNEXT technology to ensure the highest quality natural Ectoin® molecules. It is used to treat respiratory diseases, allergies, and skin conditions. Ectoin® represents a widely applicable and well-tolerated natural protective molecule that can withstand harmful environmental influences like heat, drought, or ultraviolet radiation.
Characteristics of Ectoin®
1.Stabilisation of Proteins and the structure of cells
Ectoin® stabilises biomolecules via a physical mechanism, called “preferential exclusion”. According to this theory, the protein stabilisation effects of osmo-lytes like Ectoin® are due to their effect on the solvent water leading to a prefer-ential exclusion of the osmolyte from the protein surface and thereby to a prefer-ential hydration of the protein.
Because the surface area of globular proteins in the native state is smaller than in the denatured state, the equilibrium is shifted to the native state resulting in stabilisation of the native structure.
The osmolyte promotes the formation of water molecules in clusters. Thus the exclusion hypothesis attributes the stabilising effect of Ectoin® to changes in the surrounding water structure.
Ectoin® is in contrast to e.g. sodium chloride a strongly kosmotropic (water struc- ture forming) substance. An investigation of the oxygen radial distribution func- tion of pure water, sodium chloride and Ectoin® proved the stabilising effect of Ectoin® on the water structure.
Figure 1,2,3: Effect of Ectoin® on the water structure
A:The radial distribution function of pure water shows a maximum at approx. 0.3nm,which demonstrates the direct interaction of two neighbouring water molecules. The smaller maxima at 0.45nm and 0.7nm demonstrate interactions of not neighbouring water molecules.
The addition of NaCl to water leads to a decrease in the maxima. In contrast, the solution containing Ectoin® increases the maxima and thus enhances the tetrahedral water structure.
B:Tetrahedral structure of water, showing the interactions between water molecules at 0.3nm and 0.45nm in the structure.
C:Complex formed by Ectoin® and water molecules.
Sodium chloride diminishes the interaction between water molecules. It destroys the water structure and is therefore chaotropic.
In contrast to that, a solution containing Ectoin® increases the number of neigh- bouring water molecules. Thus, Ectoin® enhances the water-water-interactions. The tetrahedral structure of water is stabilised by Ectoin®.
Figure 4: Stabilisation of biomolecules via Ectoin® according to the preferential exclusion model
Due to the exclusion of Ectoin® from the hydration shell of biopolymers, a protect-ive and stabilising shield is shaped around those biomolecules, which is termed the Ectoin® Hydro Complex. The formation of Ectoin® water complexes and thus the kosmotropic effect of Ectoin® on the water structure shown above can stabilise lipid mono- and bilayers as well, which can be considered as a model for cell membranes.
2.Membrane stabilisation and increase in membrane fluidity due to Ectoin®
Figure 5: Membrane stabilisation and increase in membrane fiuidity due to Ectoin®
A:Lipid bilayer in water: the bilayers are stabilised by hydrophilic interactions within head groups.B:Lipid bilayer in aqueous Ectoin® solution: Ectoin® water complexes cause increased interactions ofhead groups with water and the membrane fiuidity is increased.
As shown in Figure 3, a lipid bilayer in water is stabilised by hydrophobic inter-actions of the apolar lipid tail and hydrophilic interactions of the polar lipid head groups to water. In an Ectoin® solution, the hydrophilic interactions are increased by the Ectoin® water complexes resulting in increased mobility of lipids and thus fluidity of lipid bilayers.
The effect of Ectoin® on fluidity of lipid membranes was shown recently by film balance measurements of lipid monolayers (Figure 4).By increasing the surface pressure on a DPPC lipid monolayer in water the forma- tion of rigid well-shaped domains can be observed at higher pressure. These rigid domains are much smaller in Ectoin® solutions. The higher the concentration of Ectoin® the smaller the rigid domains. The effect is already observed at the lowest concentration tested (1 mM).
Figure 6: Fluorescence studies of film balance measurements
DPPC (Dipalmitoylglycerophosphatidylcholine) Monolayer at different surface pressure and Ectoin® concentrations. Rigid domains appear black, fiuid domains bright. Without Ectoin® and a surface pressure of 10mN/m, the lipid layer exists almost completely of rigid domains. With Ectoin®, more fiuid domains are visible. This effect increases with increasing Ectoin® concentration.
The physical state of the membrane influences the cell biology and its behaviour in response to external inputs. An increased fluidity of the membrane may for example induce the expression of stress-responsive, cell-protecting genes, such as heat-shock proteins, and reduce on-going inflammatory processes . The modification of the distribution of membrane proteins in a more fluid membrane also alters their activity.
An increase in the membrane fluidity could reduce disease symptoms and accel- erate healing. It is crucial for the efficient closure of wounds, and it has been suggested as mechanism for the very early effects of corticosteroids in asthma therapy and the beneficial effect of dietary moderate ethanol and polyun- saturated fatty acids intake in inflammatory diseases such as psoriasis, allergy, asthma and inflammatory bowel disease .
3.Prevention of release of stress mediators
Extracellular membrane components (transmembrane proteins, lipids, extracellular matrix) are stabilised by Ectoin® in their native form. Without protective mechan- isms, external and internal noxa can cause increased stress for cell membranes. Cells which are in direct contact with the environment like squamous epithelial cells, i.e. skin, upper airway, lung, and intestinal tract, are particularly endangered. The external stress leads to membrane damage, which causes water loss and in- flammatory reactions in the tissue.
The Ectoin® Hydro Complex protects the cells against dehydration by accumulating water. Water molecules are bound more effectively near the membranes and form a stabilising and protecting complex. The impact of external pollutants on the cells is decreased by the stabilising effect of the Ectoin® Hydro Complex. It protects the cells from inflammation caused by environmental stress factors like dehydration, UV radiation, tensides or airborne particles.
Picture 7 : Prevention of release of stress mediators (e.g. ceramides) by Ectoin®.
A:Without Ectoin® : external stress factors (like UV irradiation) cause membrane damage, water loss and release of stress mediators, which act as second messengers for infiammatory reactions.B:With Ectoin® : the Ectoin® Hydro Complex protects the membrane against external stress factors; stress mediator releasse is prevented.
Ectoin® helps skin resist external damage
Ectoin® natural is a highly hydrophilic substance with cosmotropic properties, which can increase the number of adjacent water molecules and strengthen the cross-linking structure of water. It stabilizes and protects biomolecules (such as proteins, peptides, enzymes.) and also stabilizes and protects cell membranes. It has extensive, practical uses and product applications in the medical and cosmetic markets. This product has the highest purity specifications in the market, with multiple clinical trials and certifications such as ECOCERT COSMOS and NATRUE international natural standards, providing customers with the best quality products and complete technical services.
Ectoin® repairs particles, which can form an efficient barrier to resist the invasion of foreign molecules. In addition, it is added with ingredients such as “Symcalmin,” an oat extract developed in Germany. It is free of steroids, artificial colors, fragrances, and preservatives, suitable for long-term use. It is ideal for all age groups, including infants aged 28 days, and can be applied around the eyes without irritation, relieving itching.