Macrocyclic Supramolecular Glass: New Type of Supramolecular Transparent Materials.

Transparent materials are widely used in industries, everyday life, and scientific activities. The development of new, lightweight, and durable artificial transparent materials is a challenge in synthetic chemistry. In this study, a supramolecular approach is conceived to construct transparent glass. Cyclodextrins are selected as the building blocks for the fabrication of supramolecular glass via noncovalent polymerization. The newly formed glass displays several attractive advantages, including good thermal processability, high mechanical strength and dielectric constant, excellent visible light transparency, and good adhesion performance. Importantly, the structural characteristics of long-range disorder and short-range order are observed in cyclodextrin glass. Here a new strategy is presented for the preparation and functionalization of low-molecular-weight transparent materials.

Following the Trace of Cyclodextrins on the Selenium and Tellurium Odyssey.

There is an urgent need to develop safer and more effective modalities for the treatment of numerous pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Over the past decades, cyclodextrins (CDs) have gathered great attention as potential drug carriers due to their ability to enhance their bioactivities and properties. Likewise, selenium (Se) and tellurium (Te) have been extensively studied during the last decades due to their possible therapeutical applications. Although there is limited research on the relationship between Se and Te and CDs, herein, we highlight different representative examples of the advances related to this topic as well as give our view on the future directions of this emerging area of research. This review encompasses three different aspects of this relationship: (1) modification of the structure of the different CDs; (2) formation of host-guest interaction complexes of naïve CDs with Se and Te derivatives in order to overcome specific limitations of the latter; and (3) the use of CDs as catalysts to achieve novel Se and Te compounds.

Chiral Selectivities of Permethylated α-, ß-, and γ-Cyclodextrins Containing Gas Chromatographic Stationary Phases towards Ibuprofen and Its Derivatives.

Ibuprofen is a well-known and broadly used, nonsteroidal anti-inflammatory and painkiller medicine. Ibuprofen is a chiral compound, and its two isomers have different biological effects, therefore, their chiral separation is necessary. Ibuprofen and its derivatives were used as model compounds to establish transportable structure chiral selectivity relationships. Chiral selectors were permethylated α-, ß-, and γ-cyclodextrins containing gas chromatographic stationary phases. The chiral selectivity of ibuprofen as a free acid and its various alkyl esters (methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and isoamyl esters) derivatives were tested at different temperatures. Every tested stationary phase was capable of the chiral separations of ibuprofen in its free acid form. The less strong included S optical isomers eluted before R optical isomers in every separate case. The results offer to draw transportable guidelines for the chiral selectivity vs. analyte structures. It was recognized that the S isomers of free ibuprofen acid showed an overloading phenomenon, but the R isomer did not. The results were supported by molecular modeling studies.

Variation of Cyclodextrin (CD) Complexation with Biogenic Amine Tyramine: Pseudopolymorphs of ß-CD Inclusion vs. α-CD Exclusion, Deep Atomistic Insights.

Tyramine (TRM) is a biogenic catecholamine neurotransmitter, which can trigger migraines and hypertension. TRM accumulated in foods is reduced and detected using additive cyclodextrins (CDs) while their association characteristics remain unclear. Here, single-crystal X-ray diffraction and density functional theory (DFT) calculation have been performed, demonstrating the elusive pseudopolymorphs in ß-CD inclusion complexes with TRM base/HCl, ß-CD·0.5TRM·7.6H2O (1) and ß-CD·TRM HCl·4H2O (2) and the rare α-CD·0.5(TRM HCl)·10H2O (3) exclusion complex. Both 1 and 2 share the common inclusion mode with similar TRM structures in the round and elliptical ß-CD cavities, belong to the monoclinic space group P21, and have similar herringbone packing structures. Furthermore, 3 differs from 2, as the smaller twofold symmetry-related, round α-CD prefers an exclusion complex with the twofold disordered TRM-H+ sites. In the orthorhombic P21212 lattice, α-CDs are packed in a channel-type structure, where the column-like cavity is occupied by disordered water sites. DFT results indicate that ß-CD remains elliptical to suitably accommodate TRM, yielding an energetically favorable inclusion complex, which is significantly contributed by the ß-CD deformation, and the inclusion complex of α-CD with the TRM aminoethyl side chain is also energetically favorable compared to the exclusion mode. This study suggests the CD implications for food safety and drug/bioactive formulation and delivery.

Development of a Novel Cyclodextrin-Chitosan Polymer for an Efficient Removal of Pharmaceutical Contaminants in Aqueous Solution.

A novel polymer synthesized by grafting three cyclodextrins onto chitosan was characterized and evaluated for its potential to adsorb two pharmaceutical residues: ibuprofen and progesterone. The influence of various operational parameters, including contact time, initial molecule concentration, pH, ionic strength, and temperature, was investigated. The synthesized polymer exhibits an amorphous and porous structure with a remarkable swelling capacity of 9.5 mmol/g. It demonstrates remarkable adsorption capacities for progesterone and ibuprofen, reaching 90% and 75%, respectively. Kinetic studies reveal that the adsorption of both molecules follows a pseudo-second-order model. A DSC analysis elucidated the adsorption mechanism, which is governed by the formation of inclusion complexes and electrostatic interactions within the polymer network. The polymer's regeneration after 23 cycles demonstrates its sustainable adsorption efficiency. The combination of chitosan with three cyclodextrins opens up promising new avenues for water treatment and the removal of specific pollutants. This approach significantly improves the material's selectivity towards target pollutants, offering a significant advantage in pollution remediation applications.

Enrofloxacin Pharmaceutical Formulations through the Polymer-Free Electrospinning of ß-Cyclodextrin-oligolactide Derivatives.

Enrofloxacin (ENR), a member of the fluoroquinolone class of antibiotics, is widely used in veterinary medicine to treat bacterial infections. Like many antibiotics, ENR has limited water solubility and low bioavailability. To address these challenges, drug formulations using solid dispersions, nanosuspensions, surfactants, cocrystal/salt formation, and inclusion complexes with cyclodextrins may be employed. The approach described herein proposes the development of ENR formulations by co-electrospinning ENR with custom-prepared cyclodextrin-oligolactide (CDLA) derivatives. This method benefits from the high solubility of these derivatives, enabling polymer-free electrospinning. The electrospinning parameters were optimized to incorporate significant amounts of ENR into the CDLA nanofibrous webs, reaching up to 15.6% by weight. The obtained formulations were characterized by FTIR and NMR spectroscopy methods and evaluated for their antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. This study indicates that the presence of CDLA derivative does not inhibit the antibacterial activity of ENR, recommending these formulations for further development.

Different Effects of Strong-Bonded Water with Different Degrees of Substitution of Sodium Sulfobutylether-ß-cyclodextrin on Encapsulation.

The encapsulation of sodium sulfobutylether-ß-cyclodextrin (SBE-ß-CD) is influenced not only by the degree of substitution (DS) but also by the presence of strong-bonded water (SBW). Guests compete with SBW for positions within the cavity of SBE-ß-CD. However, the correlation between DS and SBW was not clear. This study revealed a positive correlation between DS and SBW utilizing Karl Fischer titration. The mechanism may be attributed to molecular polarizability. To explore the impact of SBW inside SBE-ß-CD with different DS on encapsulation, density functional theory was employed. Throughout the release process, an increase in enthalpy is unfavorable, while an increase in entropy favors spontaneous reaction occurrence. For SBE-ß-CD (DS = 2, 3), enthalpy increase is the primary factor, leading to the retention of SBW within the cavities and consequently hindering guest entry. In contrast, for SBE-ß-CD (DS = 4, 7), the situation differs. For SBE10-ß-CD, the influence of SBW is minimal. This study aims to elucidate the relationship between DS and SBW, as well as the effect of SBW inside SBE-ß-CD with different DS on encapsulation. It is crucial for a comprehensive understanding of the factors affecting the encapsulation of SBE-ß-CD, thereby promoting quality control and functional development of SBE-ß-CD.

Enhancement of Cognitive Function by Andrographolide-Loaded Lactose ß-Cyclodextrin Nanoparticles: Synthesis, Optimization, and Behavioural Assessment.

This study investigates whether Andrographolide-loaded Lactose ß-Cyclodextrin (ALN-ßCD) nanoparticles enhance cognitive function, particularly spatial learning and memory. The successful conjugation of lactose to ß-cyclodextrin was confirmed via 1H NMR spectroscopy, facilitating neuronal cell entry. The solvent evaporation method was used to create the nanoparticles, which were characterised for particle size, PDI, zeta potential, and drug release. The nanoparticles exhibited a size of 247.9 ± 3.2 nm, a PDI of 0.5 ± 0.02, and a zeta potential of 26.8 ± 2.5 mV. FTIR and TEM analyses, along with in vitro drug release and BBB permeability studies, confirmed their stability and efficacy. Behavioural tests, including the Elevated Plus Maze, Y-Maze, Object Recognition, and Locomotor Activity tests, demonstrated significant improvements in memory, motor coordination, and exploration time in the nanoparticle-treated groups. The group treated with ALN-ßCD at a dose of 100 mg/kg/p.o. showed superior cognitive performance compared to the group receiving free andrographolides (AG). Biochemical assays indicated a significant reduction in acetylcholinesterase activity and lipid peroxidation, suggesting increased acetylcholine levels and reduced oxidative stress. Histopathological examination showed improved neuronal function without toxicity. The results showed significant improvements (p < 0.001) in memory and cognitive abilities in experimental animals, highlighting the potential of ALN-ßCD nanoparticles as a non-invasive treatment for memory loss. These promising findings warrant further exploration through clinical trials.

7-Phenylheptanoic Acid-Hydroxypropyl ß-Cyclodextrin Complex Slows the Progression of Renal Failure in Adenine-Induced Chronic Kidney Disease Mice.

The characteristic accumulation of circulating uremic toxins, such as indoxyl sulfate (IS), in chronic kidney disease (CKD) further exacerbates the disease progression. The gut microbiota, particularly gut bacterial-specific enzymes, represents a selective and attractive target for suppressing uremic toxin production and slowing the progression of renal failure. This study investigates the role of 4-phenylbutyrate (PB) and structurally related compounds, which are speculated to possess renoprotective properties in suppressing IS production and slowing or reversing renal failure in CKD. In vitro enzyme kinetic studies showed that 7-phenylheptanoic acid (PH), a PB homologue, suppresses the tryptophan indole lyase (TIL)-catalyzed decomposition of tryptophan to indole, the precursor of IS. A hydroxypropyl ß-cyclodextrin (HPßCD) inclusion complex formulation of PH was prepared to enhance its biopharmaceutical properties and to facilitate in vivo evaluation. Prophylactic oral administration of the PH-HPßCD complex formulation reduced circulating IS and attenuated the deterioration of renal function and tubulointerstitial fibrosis in adenine-induced CKD mice. Additionally, treatment of moderately advanced adenine-induced CKD mice with the formulation ameliorated renal failure, although tissue fibrosis was not improved. These findings suggest that PH-HPßCD can slow the progression of renal failure and may have implications for preventing or managing CKD, particularly in early-stage disease.

Use of ultrasound to improve the activity of cyclodextrin glycosyltransferase in the producing of ß-cyclodextrins: Impact on enzyme activity, stability and insights into changes on enzyme macrostructure.

This work explored the impact of ultrasound (US) on the activity, stability, and macrostructural conformation of cyclodextrin glycosyltransferase (CGTase) and how these changes could maximize the production of ß-cyclodextrins (ß-CDs). The results showed that ultrasonic pretreatment (20 kHz and 38 W/L) at pH 6.0 promoted increased enzymatic activity. Specifically, after sonication at 25 °C/30 min, there was a maximum activity increase of 93 % and 68 % when biocatalysis was carried out at 25 and 55 °C, respectively. For activity measured at 80 °C, maximum increase (31 %) was observed after sonication at 25 °C/60 min. Comparatively, US pretreatment at low pH (pH = 4.0) resulted in a lower activity increase (max. 28 %). These activation levels were maintained after 24 h of storage at 8 °C, suggesting that changes on CGTase after ultrasonic pretreatment were not transitory. These pretreatments altered the conformational structure of CGTase, revealed by an up to 11 % increase in intrinsic fluorescence intensity, and resulted in macrostructural modifications, such as a decrease in particle size and polydispersion index (up to 85 % and 45.8 %, respectively). Therefore, the sonication of CGTase under specific conditions of pH, time, and temperature (especially at pH 6.0/ 30 min/ 25 °C) promotes macrostructural changes in CGTase that induce enzyme activation and, consequently, higher production of ß-CDs.

Fluorogenic Monitoring of α-Amylase in Human Urine for Straightforward Diagnosis of Pancreatic Diseases.

In this study, we developed a sensitive method for monitoring α-amylase using a fluorogenic approach based on the host-guest complexation between an amphiphilic pyrenyl derivative (1) and γ-cyclodextrins (γ-CDs). The compound 1 self-assembles into nanofibrils in aqueous solutions. Upon the introduction of γ-CD, compound 1 forms an inclusion complex with it. This complex then participates in the formation of a 2:2 complex with another complex, leading to strong excimer fluorescence. Upon interaction with α-amylase, γ-CD undergoes hydrolysis, leading to the regeneration of nanofibrils, which is accompanied by a decrease in excimer fluorescence and an increase in monomeric fluorescence. This ratiometric fluorescence color change enables the sensitive detection of low levels of α-amylase in human urine, offering a practical approach for early screening of pancreatic-related diseases.

Cyclodextrins as a Strategy for Enhancing Solubility of Therapeutic Agents for Neglected Tropical Diseases: A Systematic Review.

BACKGROUND: Neglected Tropical Diseases (NTD) are chronic infectious conditions that primarily affect marginalized populations. The chemotherapeutic arsenal available for treating NTD is limited and outdated, which poses a challenge in controlling and eradicating these diseases. This is exacerbated by the pharmaceutical industry's lack of interest in funding the development of new therapeutic alternatives. In addition, a considerable number of drugs used in NTD therapy have low aqueous solubility. To address this issue, solubility enhancement strategies, such as the use of inclusion complexes with cyclodextrins (CD) can be employed. OBJECTIVE: Therefore, this systematic review aims to present the application of CD in complexing with drugs and chemotherapeutic compounds used in the therapy of some of the most prevalent NTD worldwide and how these complexes can enhance the treatment of these diseases. METHODS: Two bibliographic databases, Science Direct and PubMed, were used to conduct the search. The selection of studies and the writing of this systematic review followed the criteria outlined by the PRISMA guidelines. RESULTS: From a total of 978 articles, 23 were selected after applying the exclusion criteria. All the studies selected were consistent with the use of CD as a strategy to increase the solubility of therapeutic agents used in NTD. CONCLUSION: The results indicate that CD can enhance the solubility of chemotherapeutic agents for the treatment of Neglected Tropical Diseases (NTD). This review presents data that clearly highlights the potential use of CD in the development of new treatments for neglected tropical diseases. It can assist in the formulation of future treatments that are more effective and safer.

Adsorption performance and mechanism of pectin modified with ß-cyclodextrin for Zn2+ and Cu2.

Removing heavy metals from aqueous solutions has drawn more and more attentions these years because of their serious global health challenge to human society. To develop an adsorbent with green, stable and high-efficiency for adsorption of heavy metals, pectin ß-cyclodextrin composite was successfully prepared and used for Zn2+ and Cu2+ adsorption for the first time. Various variables that influence the adsorption performance were explored, and the optimal adsorption conditions were determined. According to the pseudo-second-order kinetic model, the adsorption process of Zn2+ and Cu2+ by the adsorbent was mainly chemical adsorption. The adsorbent adsorption process was an exothermic and non-spontaneous process. According to the Langmuir isotherm model, the maximum adsorption capacity was 12.51 ± 0.33 and 24.98 ± 0.23 mg/g for Zn2+ and Cu2+, respectively. The FTIR, EDX and XPS results revealed that the main mechanisms of removing pollutants by adsorbent were ion exchange and coordination. In addition, electrostatic attraction and chelation were present in the adsorption process. After five adsorption desorption cycles, the pectin ß-cyclodextrin composite adsorbent still exhibited adsorption and regeneration capabilities. This study provides a low-cost, effective and simple method for preparation of modified pectin, which has excellent application potential in the removal of heavy metal ions from wastewater.

ZIF-8-wrapped AgNPs modified with ß-cyclodextrin for sensitive detection of thiacloprid and imidacloprid by SERS technology.

The high efficient surface-enhanced Raman scatterring (SERS) methods to detect thiacloprid and imidacloprid were established using ZIF-8-wrapped Ag nanoparticles (AgNPs) modified with ß-cyclodextrin (ß-CD). The substrate of ZIF-8/ß-CD@AgNPs was characterized by ultraviolet visible spectra (UV-vis), thermogravimetric analysis (TGA), X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM). The interaction between the substrate and thiacloprid/imidacloprid was also explored. The optimum measurement conditions were obtained by response surface model based on single-factor experiments. Enhancement factors (EFs) of thiacloprid and imidacloprid were respectively 2.29 × 106 and 2.60 × 106. A good linearity between the scattering intensity and the concentration of thiacloprid/imidacloprid within 3-1000 nmol L-1/6-400 nmol L-1 was established. The interference experiments indicated that the methods had good selectivity. The SERS methods were successfully applied to detect thiacloprid and imidacloprid in several vegetables samples. The recoveries ranged from 95.5 % to 105 % (n = 5). The detection limits (LODs) (S/N = 3) for thiacloprid and imidacloprid were 1.50 and 0.83 nmol L-1, respectively.

Fabrication of a salivary amylase electrochemical sensor based on surface confined MWCNTs/ß-cyclodextrin/starch architect for dental caries in clinical samples.

Salivary α-amylase (α-ALS) has drawn attention as a possible bioindicator for dental caries. Herein, combining the synergistic properties of multi-walled carbon nanotubes (MWCNTs), ß-cyclodextrin (ß-CD) and starch, an electrochemical sensor is constructed employing ferrocene (FCN) as an electrochemical indicator to oversee the progression of the enzymatic catalysis of α-ALS. The method involves a two-step chemical reaction sequence on a screen-printed carbon electrode (SPCE). X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscope (FE-SEM), and Dynamic light scattering (DLS) were used to characterize the synthesized material, while Static water Contact angle measurements, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) were performed to monitor each step of sensor fabrication. The electrochemical sensor permitted to detect α-ALS within the linear range of 0.5-280 U mL-1, revealing detection (LOD), and quantification (LOQ) values of 0.041 U mL-1, and 0.159 U mL-1, respectively. Remarkably, the sensor demonstrated exceptional specificity and selectivity, effectively discriminating against other interfering substances in saliva. Validation of the method involved analyzing α-ALS levels in artificial saliva with an accuracy range of 97 % to 103 %, as well as in real clinical saliva samples across various age groups.

Cyclodextrin-modified PVDF membranes with improved anti-fouling performance.

The design of hydrophilic polyvinylidene fluoride (PVDF) membranes with anti-fouling properties has been explored for decades. Surface modification and blending are typical strategies to tailor the hydrophilicity of PVDF membranes. Herein, cyclodextrin was used to improve the antifouling performance of PVDF membranes. Cyclodextrin-modified PVDF membranes were prepared by coupling PVDF amination (blending with branched polyethyleneimine) and activated cyclodextrin grafting. The blending of PEI in the PVDF casting solution preliminarily aminated the PVDF, resulting in PEI-crosslinked/grafted PVDF membranes after phase inversion. Aldehydes groups on cyclodextrin, introduced by oxidation, endow cyclodextrin to be grafted on the aminated PVDF membrane by the formation of imines. Borch reduction performed on the activated cyclodextrin-grafted PVDF membrane converted the imine bonds to secondary amines, ensuring the membrane stability. The resulting membranes possess excellent antifouling performance, with a lower protein adsorption capacity (5.7 µg/cm2, indicated by Bovine Serum Albumin (BSA)), and a higher water flux recovery rate (FRR = 96%). The proposed method provides a facial strategy to prepare anti-fouling PVDF membranes.

ß-Cyclodextrin-based nanoassemblies for the treatment of atherosclerosis.

Atherosclerosis, a chronic and progressive condition characterized by the accumulation of inflammatory cells and lipids within artery walls, remains a leading cause of cardiovascular diseases globally. Despite considerable advancements in drug therapeutic strategies aimed at managing atherosclerosis, more effective treatment options for atherosclerosis are still warranted. In this pursuit, the emergence of ß-cyclodextrin (ß-CD) as a promising therapeutic agent offers a novel therapeutic approach to drug delivery targeting atherosclerosis. The hydrophobic cavity of ß-CD facilitates its role as a carrier, enabling the encapsulation and delivery of various therapeutic compounds to affected sites within the vasculature. Notably, ß-CD-based nanoassemblies possess the ability to reduce cholesterol levels, mitigate inflammation, solubilize hydrophobic drugs and deliver drugs to affected tissues, making these nanocomponents promising candidates for atherosclerosis management. This review focuses on three major classes of ß-CD-based nanoassemblies, including ß-CD derivatives-based, ß-CD/polymer conjugates-based and polymer ß-CD-based nanoassemblies, highlighting a variety of formulations and assembly methods to improve drug delivery and therapeutic efficacy. These ß-CD-based nanoassemblies exhibit a variety of therapeutic mechanisms for atherosclerosis and offer systematic strategies for overcoming barriers to drug delivery. Finally, we discuss the present obstacles and potential opportunities in the development and application of ß-CD-based nanoassemblies as novel therapeutics for managing atherosclerosis and addressing cardiovascular diseases.

Research progress of fluorescent composites based on cyclodextrins: Preparation strategies, fluorescence properties and applications in sensing and bioimaging.

Fluorescence analysis has been regarded as one of the commonly used analytical methods because of its advantages of simple operation, fast response, low cost and high sensitivity. So far, various fluorescent probes, with noble metal nanoclusters, quantum dots, organic dyes and metal organic frameworks as representatives, have been widely reported. However, single fluorescent probe often suffers from some deficiencies, such as low quantum yield, poor chemical stability, low water solubility and toxicity. To overcome these disadvantages, the introduction of cyclodextrins into fluorescent probes has become a fascinating approach. This review (with 218 references) systematically covers the research progress of fluorescent composites based on cyclodextrins in recent years. Preparation strategies, fluorescence properties, response mechanisms and applications in sensing (ions, organic pollutants, bio-related molecules, temperature, pH) and bioimaging of fluorescent composites based on cyclodextrins are summarized in detail. Finally, the current challenges and future perspectives of these composites in relative research fields are discussed.

Evaluation of functional transbilayer coupling in live cells by controlled lipid exchange and imaging fluorescence correlation spectroscopy.

Biophysical coupling between the inner and outer leaflets, known as inter-leaflet or transbilayer coupling, is a fundamental organizational principle in the plasma membranes of live mammalian cells. Lipid-based interactions between the two leaflets are proposed to be a primary mechanism underlying transbilayer coupling. However, there are only a few experimental evidence supporting the existence of such interactions in live cells. This is seemingly due to the lack of experimental strategies to perturb the lipid composition in one leaflet and quantitative techniques to evaluate the biophysical properties of the opposite leaflet. The existing strategies often dependent on immobilization and clustering a component in one of the leaflets and technically demanding biophysical tools to evaluate the effects on the opposing leaflet. In the recent years, the London group developed a simple but elegant method, namely methyl-alpha-cyclodextrin catalyzed lipid exchange (LEX), to efficiently exchange outer leaflet lipids with an exogenous lipid of choice. Here, we adopted this method to perturb outer leaflet lipid composition. The corresponding changes in the inner leaflet is evaluated by comparing the diffusion of lipid probes localized in this leaflet in unperturbed and perturbed conditions. We employed highly multiplexed imaging fluorescence correlation spectroscopy (ImFCS), realized in a commercially available or home-built total internal reflection fluorescence microsocope equipped with a fast and sensitive camera, to determine diffusion coefficient of the lipid probes. Using the combination of LEX and ImFCS, we directly demonstrate lipid-based transbilayer coupling that does not require immobilization of membrane components in live mast cells in resting conditions. Overall, we present a relatively straightforward experimental strategy to evaluate transbilayer coupling quantitively in live cells.

MαCD-based plasma membrane outer leaflet lipid exchange in mammalian cells to study insulin receptor activity.

Signaling receptors on the plasma membrane, such as insulin receptor, can have their activity modulated to some extent by their surrounding lipids. Studying the contribution of membrane lipid properties such as presence of ordered lipid domains or bilayer thickness on the activity of receptors has been a challenging objective in living cells. Using methyl-alpha cyclodextrin-mediated lipid exchange, we are able to alter the lipids of the outer leaflet plasma membrane of mammalian cells to investigate the effect of the properties of the exchanged lipid upon receptor function in live cells. In this article, we describe the technique of lipid exchange in detail and how it can be applied to better understand lipid-mediated regulation of insulin receptor activity in cells.