Biological Membranes Research Articles

Chemistry meets biology in the coordination dynamics of metalloproteins

Metal sites in proteins are often presented in an idealized way that does not capture the intrinsic dynamic behavior of the protein or the extrinsic factors that affect changes in the coordination of the metal ion in biological space and time. The bioinorganic chemistry possible in healthy and diseased living organisms is limited by prevailing pH values, redox potentials, and availability and concentrations of metal ions and ligands. Changes in any of these parameters and protein-protein or protein-ligand interactions can result in differences in the type of metal ion bound, metal occupancy, and coordination number or geometry. This article addresses the plasticity and complexity of metal coordination in proteins when these parameters are considered. It uses three examples of zinc sites with sulfur donor atoms from cysteines in mammalian proteins: alcohol dehydrogenases, metallothioneins, and zinc transporters of the ZnT (SLC30A) family. Coordination dynamics of the metal sites in these proteins has different purposes; in alcohol dehydrogenases for the metal ion to perform its different roles in the catalytic cycle, in metallothioneins for serving as a metal buffer, and in ZnT zinc transporters for sensing metal ions and moving them through the protein and thus biological membranes. Defining the biological and chemical parameters that determine and affect coordination dynamics of metal ions in proteins will inform future investigations of metalloproteins.

The Future of Painless Injection: Exploring the Materials Used, Manufacturing Materials and It’s Applications in Transdermal Drug Delivery System

This article review’s about the high barrier qualities of biological membranes, such as the stratum corneum (SC) of the skin or the sclera/cornea of the eye, among others, many therapeutic medicines that have the potential to be very effective are constrained by their inability to reach the systemic circulation. The SC, the skin's outermost layer, serves as the main deterrent to drugs given topically. Thus, the intact SC acts as the body's primary defense against foreign chemicals, such as pharmaceuticals. The only medications that can be successfully supplied transdermally are those with very particular physicochemical characteristics (molecular weight 500 Da, sufficient lipophilicity, and low melting point). It is difficult to administer hydrophilic medications and macromolecular targets including peptides, DNA, and small interfering RNA transdermally. Therefore, bypass or reversible disruption may be used to facilitate medication penetration through the SC. When used to penetrate skin, microneedles (MNs) will bypass the SC, form temporary micron-sized aqueous transport channels, and increase transdermal permeability. Since these micro pores are several orders of magnitude larger than molecular dimensions, hydrophilic macromolecules should easily be able to go through them. Many research teams and pharmaceutical businesses around the world have used different methods to create MNs. This review describes different MN types and fabrication processes.

Classification of SLC family-related genes involved in ferroptosis predicts lung cancer prognosis and immunotherapy response

Lung adenocarcinoma, the most frequent type of lung cancer, is the leading cause of cancer-related deaths worldwide. Ferroptosis, controlled cell death that involves a high degree of iron-dependent lipid peroxidation, has been linked to tumor therapy sensitivity, patient prognosis, and cancer development. The solute carrier superfamily has over 400 members and comprises the largest class of transporters in the human genome. Solute carrier proteins can facilitate the movement of different substrates across biological membranes, which is crucial for physiological activities, including ferroptosis. Here, we developed a new model to further explore the role of the solute carrier family in ferroptosis in the lung adenocarcinoma immunological milieu. We used consensus clustering to classify patients with lung cancer into two subgroups (cluster1 and cluster2). Patients in the cluster1 subtype had a better prognosis and higher immune cell infiltration ratios than those in the cluster2 subtype. Furthermore, to evaluate the prognosis, the immune cell infiltration ratio, and the medication sensitivity of patients with lung adenocarcinoma, we developed gene scores related to the solute carrier family. In conclusion, we successfully developed a model incorporating the solute carrier family and ferroptosis to predict survival and the impact of immunotherapy on patients with lung cancer.

SPANA: Spatial decomposition analysis for cellular-scale molecular dynamics simulations.

The rapid increase in computational power with the latest supercomputers has enabled atomistic molecular dynamics (MDs) simulations of biomolecules in biological membrane, cytoplasm, and other cellular environments. These environments often contain a million or more atoms to be simulated simultaneously. Therefore, their trajectory analyses involve heavy computations that can become a bottleneck in the computational studies. Spatial decomposition analysis (SPANA) is a set of analysis tools in the Generalized-Ensemble Simulation System (GENESIS) software package that can carry out MD trajectory analyses of large-scale biological simulations using multiple CPU cores in parallel. SPANA applies the spatial decomposition of a large biological system to distribute structural and dynamical analyses into individual CPU cores, which reduces the computational time and the memory size, significantly. SPANA opens new possibilities for detailed atomistic analyses of biomacromolecules as well as solvent water molecules, ions, and metabolites in MD simulation trajectories of very large biological systems containing more than millions of atoms in cellular environments.

Analysis of Carica papaya Informs Lineage-Specific Evolution of the Aquaporin (AQP) Family in Brassicales.

Aquaporins (AQPs), a type of intrinsic membrane proteins that transport water and small solutes across biological membranes, play crucial roles in plant growth and development. This study presents a first genome-wide identification and comparative analysis of the AQP gene family in papaya (Carica papaya L.), an economically and nutritionally important fruit tree of tropical and subtropical regions. A total of 29 CpAQP genes were identified, which represent five subfamilies, i.e., nine plasma intrinsic membrane proteins (PIPs), eight tonoplast intrinsic proteins (TIPs), seven NOD26-like intrinsic proteins (NIPs), two X intrinsic proteins (XIPs), and three small basic intrinsic proteins (SIPs). Although the family is smaller than the 35 members reported in Arabidopsis, it is highly diverse, and the presence of CpXIP genes as well as orthologs in Moringa oleifera and Bretschneidera sinensis implies that the complete loss of the XIP subfamily in Arabidopsis is lineage-specific, sometime after its split with papaya but before Brassicaceae-Cleomaceae divergence. Reciprocal best hit-based sequence comparison of 530 AQPs and synteny analyses revealed that CpAQP genes belong to 29 out of 61 identified orthogroups, and lineage-specific evolution was frequently observed in Brassicales. Significantly, the well-characterized NIP3 group was completely lost; lineage-specific loss of the NIP8 group in Brassicaceae occurred sometime before the divergence with Cleomaceae, and lineage-specific loss of NIP2 and SIP3 groups in Brassicaceae occurred sometime after the split with Cleomaceae. In contrast to a predominant role of recent whole-genome duplications (WGDs) on the family expansion in B. sinensis, Tarenaya hassleriana, and Brassicaceae plants, no recent AQP repeats were identified in papaya, and ancient WGD repeats are mainly confined to the PIP subfamily. Subfamily even group-specific evolution was uncovered via comparing exon-intron structures, conserved motifs, the aromatic/arginine selectivity filter, and gene expression profiles. Moreover, down-regulation during fruit ripening and expression divergence of duplicated CpAQP genes were frequently observed in papaya. These findings will not only improve our knowledge on lineage-specific family evolution in Brassicales, but also provide valuable information for further studies of AQP genes in papaya and species beyond.

Brownian Aging as One of the Mechanistic Components That Shape the Single-Channel Ionic Currents through Biological and Synthetic Membranes.

Semipermeable membranes enable the separation of a given system from its environment. In biological terms, they are responsible for cells' identity. In turn, the functioning of ion channels is crucial for the control of ionic fluxes across the membranes and, consequently, for the exchange of chemical and electrical signals. This paper presents a model and simulations of currents through ionic nanochannels in an attempt to better understand the physical mechanism(s) of open/closed (O/C) sequences, i.e., random interruptions of ionic flows through channels observed in all known biochannels and in some synthetic nanopores. We investigate whether aging, i.e., the changes in Brownian motion characteristics with the lapse of time, may be at least one of the sources of the O/C sequences (in addition to the gating machinery in biochannels). The simulations based on the approximated nanostructure of ion channels confirm this postulation. The results also show the possibility of changing the O/C characteristics through an appropriate alteration of the channel surroundings. This observation may be valuable in technical uses of nanochannels in synthetic membranes and allow for a better understanding of the reason for the differences between the biochannels' activity in diverse biological membranes. Proposals of experimental verification of this aging O/C hypothesis are also presented.

Coenzyme Q in Thraustochytrium sp. RT2316-16: Effect of the Medium Composition.

Coenzyme Q (CoQ; ubiquinone) is an essential component of the respiratory chain. It is also a potent antioxidant that prevents oxidative damage to DNA, biological membranes, and lipoproteins. CoQ comprises a six-carbon ring with polar substituents that interact with electron acceptors and donors, and a hydrophobic polyisoprenoid chain that allows for its localization in cellular membranes. Human CoQ has 10 isoprenoid units (CoQ10) within the polyisoprenoid chain. Few microorganisms produce CoQ10. This work shows that Thraustochytrium sp. RT2316-16 produces CoQ10 and CoQ9. The CoQ10 content in RT2316-16 depended strongly on the composition of the growth medium and the age of the culture, whereas the CoQ9 content was less variable probably because it served a different function in the cell. Adding p-hydroxybenzoic acid to the culture media positively influenced the CoQ10 content of the cell. The absence of some B vitamins and p-aminobenzoic acid in the culture medium negatively affected the growth of RT2316-16, but reduced the decline in CoQ10 that otherwise occurred during growth. The highest content of CoQ9 and CoQ10 in the biomass were 855 μg g-1 and 10 mg g-1, respectively. The results presented here suggest that the thraustochytrid RT2316-16 can be a potential vehicle for producing CoQ10. Metabolic signals that trigger the synthesis of CoQ10 in RT2316-16 need to be determined for optimizing culture conditions.

The Application of Prodrugs as a Tool to Enhance the Properties of Nucleoside Reverse Transcriptase Inhibitors.

Antiretroviral Therapy (ART) is an effective treatment for human immunodeficiency virus (HIV) which has transformed the highly lethal disease, acquired immunodeficiency syndrome (AIDS), into a chronic and manageable condition. However, better methods need to be developed for enhancing patient access and adherence to therapy and for improving treatment in the long term to reduce adverse effects. From the perspective of drug discovery, one promising strategy is the development of anti-HIV prodrugs. This approach aims to enhance the efficacy and safety of treatment, promoting the development of more appropriate and convenient systems for patients. In this review, we discussed the use of the prodrug approach for HIV antiviral agents and emphasized nucleoside reverse transcriptase inhibitors. We comprehensively described various strategies that are used to enhance factors such as water solubility, bioavailability, pharmacokinetic parameters, permeability across biological membranes, chemical stability, drug delivery to specific sites/organs, and tolerability. These strategies might help researchers conduct better studies in this field. We also reported successful examples from the primary therapeutic classes while discussing the advantages and limitations. In this review, we highlighted the key trends in the application of the prodrug approach for treating HIV/AIDS.

Initial Quenching Efficiency Determines Light-Driven H2 Evolution of [Mo3 S13 ]2- in Lipid Bilayers.

Nature uses reactive components embedded in biological membranes to perform light-driven photosynthesis. Here, a model artificial photosynthetic system for light-driven hydrogen (H2 ) evolution is reported. The system is based on liposomes where amphiphilic ruthenium trisbipyridine based photosensitizer (RuC9 ) and the H2 evolution reaction (HER) catalyst [Mo3 S13 ]2- are embedded in biomimetic phospholipid membranes. When DMPC was used as the main lipid of these light-active liposomes, increased catalytic activity (TONCAT ~200) was observed compared to purely aqueous conditions. Although all tested lipid matrixes, including DMPC, DOPG, DPPC and DOPG liposomes provided similar liposomal structures according to TEM analysis, only DMPC yielded high H2 amounts. In situ scanning electrochemical microscopy (SECM) measurements using Pd microsensors revealed an induction period of around 26 minutes prior to H2 evolution, indicating an activation mechanism which might be induced by the fluid-gel phase transition of DMPC at room temperature. Stern-Volmer-type quenching studies revealed that electron transfer dynamics from the excited state photosensitizer are most efficient in the DMPC lipid environment giving insight for design of artificial photosynthetic systems using lipid bilayer membranes.

STRUCTURAL AND FUNCTIONAL ASPECTS OF THE INTERACTIONS BETWEEN MEDICAL POLYMERS AND THE LIPOSOMS AND BACTERIAL CELLS

Polymers are widely applied as drug delivery systems and implant coatings. The review is devoted to the mechanisms of interaction of biomedical polymers with model cell membranes (liposomes) and real biological objects - bacterial cell surfaces. A comparative analysis of the composition, structure and surface charge of different types of biological membranes has been outlined. We consider the main methods and approaches for studying the effect of polymers on the structure and physico-chemical properties of membranes to uncover adsorption, defects in the bilayer, violations of the integrity of the bilayer, changes in cell morphology, etc. The correlation between the observed effects on model and real objects is analyzed. One of the important tasks of the review is to discover the key polymer’s characteristic (structure, size, charge, etc.) for the design of new high-molecular compounds with specified biological properties.

The role and mechanism of biological collagen membranes in repairing cartilage injury through the p38MAPK signaling pathway

ObjectiveTo explore the mechanism of the p38MAPK signaling pathway in repairing articular cartilage defects with biological collagen membranes.MethodsThirty-two healthy adult male rabbits were randomly divided into a control group (n = 8), model group (n = 8), treatment group (n = 8) and positive drug group (n = 8). The control group was fed normally, and the models of bilateral knee joint femoral cartilage defects were established in the other three groups. The knee cartilage defects in the model group were not treated, the biological collagen membrane was implanted in the treatment group, and glucosamine hydrochloride was intragastrically administered in the positive drug group. Twelve weeks after the operation, the repair of cartilage defects was evaluated by histological observation (HE staining and Masson staining), the degree of cartilage repair was quantitatively evaluated by the Mankin scoring system, the mRNA expression levels of p38MAPK, MMP1 and MMP13 were detected by real-time fluorescence quantitative PCR (qRT-PCR), and the protein expression levels of p38MAPK, p-p38MAPK, MMP1 and MMP13 were detected by Western blotting. The results after the construction of cartilage defects, histological staining showed that the articular cartilage wound was covered by a large capillary network, the cartilage tissue defect was serious, and a small amount of collagen fibers were formed around the wound, indicating the formation of a small amount of new bone tissue. In the treatment group and the positive drug group, the staining of cartilage matrix was uneven, the cytoplasmic staining was lighter, the chondrocytes became hypertrophic as a whole, the chondrocytes cloned and proliferated, some areas were nest-shaped, the cells were arranged disorderly, the density was uneven, and the nucleus was stained deeply. The Mankin score of the model group was significantly higher than that of the control group, while the Mankin scores of the treatment group and positive drug group were significantly lower than that of the model group. The results of qRT-PCR detection showed that compared with the control group, the expression level of the p38MAPK gene in the model group did not increase significantly, but the gene expression levels of MMP1 and MMP13 in the model group increased significantly, while the gene expression levels of MMP1 and MMP13 decreased significantly in the treatment group and positive drug group compared with the model group. The results of Western blot detection showed that compared with the control group, the expression level of p38MAPK protein in the model group was not significantly increased, but the phosphorylation level of p38MAPK protein and the protein expression levels of MMP1 and MMP13 were significantly increased in the model group, while the phosphorylation level of p38MAPK protein and the protein expression levels of MMP1 and MMP13 in the treatment group and positive drug group were significantly lower than those in the model group.ConclusionThe biological collagen membrane can regulate the expression of MMP1 and MMP13 and repair the activity of chondrocytes by reducing the phosphorylation level of p38MAPK and inhibiting the activation of the p38MAPK signaling pathway, thus improving the repair effect of articular cartilage defects in rabbits. The P38MAPK signaling pathway is expected to become an important molecular target for the clinical treatment of cartilage defects in the future.

The underlying mechanical properties of membranes tune their ability to fuse

Membrane fusion is a ubiquitous process associated with a multitude of biological events. Although it has long been appreciated that membrane mechanics plays an important role in membrane fusion, the molecular interplay between mechanics and fusion has remained elusive. For example, although different lipids modulate membrane mechanics differently, depending on their composition, molar ratio, and complex interactions, differing lipid compositions may lead to similar mechanical properties. This raises the question of whether (i) the specific lipid composition or (ii) the average mesoscale mechanics of membranes acts as the determining factor for cellular function. Furthermore, little is known about the potential consequences of fusion on membrane disruption. Here, we use a combination of confocal microscopy, time-resolved imaging, and electroporation to shed light onto the underlying mechanical properties of membranes that regulate membrane fusion. Fusion efficiency follows a nearly universal behavior that depends on membrane fluidity parameters, such as membrane viscosity and bending rigidity, rather than on specific lipid composition. This helps explaining why the charged and fluid membranes of the inner leaflet of the plasma membrane are more fusogenic than their outer counterparts. Importantly, we show that physiological levels of cholesterol, a key component of biological membranes, has a mild effect on fusion but significantly enhances membrane mechanical stability against pore formation, suggesting that its high cellular levels buffer the membrane against disruption. The ability of membranes to efficiently fuse while preserving their integrity may have given evolutionary advantages to cells by enabling their function while preserving membrane stability.

Cloning and Overexpressing Membrane Proteins Using Pichia pastoris (Komagataella phaffii)

AbstractUnderstanding the structure and function of key proteins located within biological membranes is essential for fundamental knowledge and therapeutic applications. Robust cell systems allowing their actual overexpression are required, among which stands the methylotrophic yeast Pichia pastoris. This system proves highly efficient in producing many eukaryotic membrane proteins of various functions and structures at levels and quality compatible with their subsequent isolation and molecular investigation. This article describes a set of basic guidelines and directions to clone and select recombinant P. pastoris clones overexpressing eukaryotic membrane proteins. Illustrative results obtained for a panel of mammalian membrane proteins are presented, and hints are given on a series of experimental parameters that may substantially improve the amount and/or the functionality of the expressed proteins. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Designing and cloning a P. pastoris expression vectorBasic Protocol 2: Integrative transformation of P. pastoris and selection of recombinant clonesBasic Protocol 3: Culturing transformed P. pastoris for membrane protein expressionBasic Protocol 4: Yeast cell lysis and membrane preparationBasic Protocol 5: Immunodetection of expressed membrane proteins: western blotAlternate Protocol 1: Immunodetection of expressed membrane proteins: dot blotAlternate Protocol 2: Immunodetection of expressed membrane proteins: yeastern blotBasic Protocol 6: Activity assay: ligand‐binding analysis of an expressed GPCR

X-ray study of structural changes in “di-(2-ethylhexyl) sulfosuccinic acid (AOT) /n-heptane-water” liquid crystalline system depending on the concentration of components

Structural changes in the “sodium salt of di-(2-ethylhexyl)sulfosuccinic acid (AOT) - n-heptane-water” liquid-crystalline system depending on the AOT concentration in the n-heptane-water mixed solvent were studied using the X-ray diffraction method. The studies were carried out in a wide range of the AOT concentrations from 27 to 92% in a mixed solvent n-heptane/water=5.8 ratio.The mesomorphism of a liquid-crystalline system is on the concentration of the system. It is confirmed that at concentrations the AOT above 50%, a liquid crystal structure with an intradomain "flat" liquid crystal layered phase takes place. A “flat” lamellar lyotropic-liquid-crystalline phase with an intradomain lamellar structure is formed in the system. The structural parameters, the compactness of the liquid crystal system, the thickness of the formed layers, the surface area per molecular head on the surface of the layers depending on the concentration and thickness of the bound water layer are revealed. The liquid crystal system under study can serve as a model for studying various problems of biological membranes.

Nonlinear Cell Deformation Model

Abstract Cytoskeletal mechanics is a field that heavily relies on mathematical models to interpret experimental data related to forces and deformations. In this paper, we present a novel mathematical model designed specifically for analysing the mechanical properties of liposomes, which serve as model systems for studying biological membranes. Our model takes into account various factors such as stretching, bending, and contact adhesion during atomic force microscopy (AFM) indentation using a spherical tip. By applying our model to liposomes, we demonstrate that these structures exhibit nonlinear behaviour characterized by low stiffness at small deformations. Furthermore, we find that the mechanical response of liposomes is influenced by their size. Additionally, we observe that the presence of adhesion energy contributes to the generation of negative tip forces upon initial contact.

Adhesions in the setting of hip arthroscopy

With the growing number of primary arthroscopies performed, patients requiring revision hip arthroscopies for various issues is high including postoperative adhesion formation, a source of pain, mechanical symptoms, range of motion limitation, stiffness, and microinstability. Adhesions are a consequence of biological pathways that have been stimulated by injury or surgical interventions leading to an increased healing response. Preventative efforts have included surgical adjuncts during/after primary hip arthroscopy, biologic augmentation, and postoperative rehabilitation. Treatment options for adhesion formation includes surgical lysis of adhesions with or without placement of biologic membranes aimed at inhibiting adhesion reformation as well as systemic medications to further reduce the risk. Postoperative rehabilitation exercises have also been demonstrated to prevent adhesions as a result of hip arthroscopy. Ongoing clinical trials are further investigating pathways and prevention of adhesion formation.

Model Problems on Oscillations of Mechanical and Biological Membranes

Various models of membrane oscillations emerging in the theory of elasticity of mechanical systems, biomechanics of the internal ear of vertebrata, and in the theory of electrical circuits are discussed in the article. The considered oscillations have different natures, but their mathematical models are described using similar initial boundary value problems for the second-order hyperbolic equation with the nontrivial boundary condition. The differential equations in these problems are the same. Thus, for example, the model of voltage distribution in the telegraph line emerges for the one-dimensional equation of oscillations. The model of oscillations of a circular homogeneous solid membrane, a membrane with a hole, and the model of gas oscillations in a sphere and spherical region emerge for the two-dimensional and three-dimensional operators, but take into account the radial symmetry of oscillations. The model problem on membrane oscillation can be considered as the problem on ear drum membrane oscillations. The unified approach to reducing the corresponding problems to the initial boundary value problem with zero boundary conditions is suggested. The technique of formulating the solution in the form of a Fourier series using eigenfunctions of the corresponding Sturm–Liouville problem is described.

Investigation of nano- and microdomains formed by ceramide 1 phosphate in lipid bilayers

Biological membranes are renowned for their intricate complexity, with the formation of membrane domains being pivotal to the successful execution of numerous cellular processes. However, due to their nanoscale characteristics, these domains are often understudied, as the experimental techniques required for quantitative investigation present significant challenges. In this study we employ spot-variation z-scan fluorescence correlation spectroscopy (svzFCS) tailored for artificial lipid vesicles of varying composition and combine this approach with high-resolution imaging. This method has been harnessed to examine the lipid-segregation behavior of distinct types of ceramide-1-phosphate (C1P), a crucial class of signaling molecules, within these membranes. Moreover, we provide a quantitative portrayal of the lipid membranes studied and the domains induced by C1P at both nano and microscales. Given the lack of definitive conclusions from the experimental data obtained, it was supplemented with comprehensive in silico studies—including the analysis of diffusion coefficient via molecular dynamics and domain populations via Monte Carlo simulations. This approach enhanced our insight into the dynamic behavior of these molecules within model lipid membranes, confirming that nano- and microdomains can co-exist in lipid vesicles.

Tetraspanner-based nanodomains modulate BAR domain-induced membrane curvature.

The topography of biological membranes is critical for formation of protein and lipid microdomains. One prominent example in the yeast plasma membrane (PM) are BAR domain-induced PM furrows. Here we report a novel function for the Sur7 family of tetraspanner proteins in the regulation of local PM topography. Combining TIRF imaging, STED nanoscopy, freeze-fracture EM and membrane simulations we find that Sur7 tetraspanners form multimeric strands at the edges of PM furrows, where they modulate forces exerted by BAR domain proteins at the furrow base. Loss of Sur7 tetraspanners or Sur7 displacement due to altered PIP2 homeostasis leads to increased PM invagination and a distinct form of membrane tubulation. Physiological defects associated with PM tubulation are rescued by synthetic anchoring of Sur7 to furrows. Our findings suggest a key role for tetraspanner proteins in sculpting local membrane domains. The maintenance of stable PM furrows depends on a balance between negative curvature at the base which is generated by BAR domains and positive curvature at the furrows' edges which is stabilized by strands of Sur7 tetraspanners.

Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids

Biological membranes, primarily composed of lipids, envelop each living cell. The intricate composition and organization of membrane lipids, including the variety of fatty acids they encompass, serve a dynamic role in sustaining cellular structural integrity and functionality. Typically, modifications in lipid composition coincide with consequential alterations in universally significant signaling pathways. Exploring the various fatty acids, which serve as the foundational building blocks of membrane lipids, provides crucial insights into the underlying mechanisms governing a myriad of cellular processes, such as membrane fluidity, protein trafficking, signal transduction, intercellular communication, and the etiology of certain metabolic disorders. Furthermore, comprehending how alterations in the lipid composition, especially concerning the fatty acid profile, either contribute to or prevent the onset of pathological conditions stands as a compelling area of research. Hence, this review aims to meticulously introduce the intricacies of membrane lipids and their constituent fatty acids in a healthy organism, thereby illuminating their remarkable diversity and profound influence on cellular function. Furthermore, this review aspires to highlight some potential therapeutic targets for various pathological conditions that may be ameliorated through dietary fatty acid supplements. The initial section of this review expounds on the eukaryotic biomembranes and their complex lipids. Subsequent sections provide insights into the synthesis, membrane incorporation, and distribution of fatty acids across various fractions of membrane lipids. The last section highlights the functional significance of membrane-associated fatty acids and their innate capacity to shape the various cellular physiological responses.