We show that the activity of an ion channel is strictly related to the phase state of the lipid bilayer hosting the channel. By measuring unitary conductance, dwell times, and open probability of the K+ channel KcsA as a function of temperature in lipid bilayers composed of POPE and POPG in different relative proportions, we obtain that all those properties show a trend inversion when the bilayer is in the transition region between the liquid disordered and the solid ordered phase. These data suggest that the physical properties of the lipid bilayer influence ion channel activity likely via a fine tuning of its conformations. In a more general interpretative framework, we suggest that other parameters such as pH, ionic strength, and the action of amphiphilic drugs can affect the physical behavior of the lipid bilayer in a fashion similar to temperature changes resulting in functional changes of transmembrane proteins.
In this article we compare electrical conductance events from single channel recordings of three TRP channel proteins (TRPA1, TRPM2 and TRPM8) expressed in human embryonic kidney cells with channel events recorded on synthetic lipid membranes close to melting transitions. Ion channels from the TRP family are involved in a variety of sensory processes including thermo- and mechano-reception. Synthetic lipid membranes close to phase transitions display channel-like events that respond to stimuli related to changes in intensive thermodynamic variables such as pressure and temperature. TRP channel…
Synthetic lipid membranes can display channel-like ion conduction events even in the absence of proteins. We show here that these events are voltage-gated with a quadratic voltage dependence as expected from electrostatic theory of capacitors. To this end, we recorded channel traces and current histograms in patch-experiments on lipid membranes. We derived a theoretical current-voltage relationship for pores in lipid membranes that describes the experimental data very well when assuming an asymmetric membrane. We determined the equilibrium constant between closed and open state and the open pr…
The interpretation electrical phenomena in biomembranes is usually based on the assumption that the experimentally found discrete ion conduction events are due to a particular class of proteins called ion channels while the lipid membrane is considered being an inert electrical insulator. The particular protein structure is thought to be related to ion specificity, specific recognition of drugs by receptors and to macroscopic phenomena as nerve pulse propagation. However, lipid membranes in their chain melting regime are known to be highly permeable to ions, water and small molecules, and are …
Amyloid beta peptides (A\b{eta}), implicated in Alzheimers disease (AD), interact with the cellular membrane and induce amyloid toxicity. The composition of cellular membranes changes in aging and AD. We designed multi component lipid models to mimic healthy and diseased states of the neuronal membrane. Using atomic force microscopy (AFM), Kelvin probe force microscopy (KPFM) and black lipid membrane (BLM) techniques, we demonstrated that these model membranes differ in their nanoscale structure and physical properties, and interact differently with A\b{eta}. Based on our data, we propose a ne…
There is mounting evidence that lipid bilayers display conductive properties. However, when interpreting the electrical response of biological membranes to voltage changes, they are commonly considered as inert insulators. However, lipid bilayers under voltage-clamp conditions do not only display current traces with discrete conduction-steps indistinguishable from those attributed to the presence of protein channels. In current-voltage (I-V) plots they may also display outward rectification, i.e., voltage-gating. Surprisingly, this has even been observed in chemically symmetric lipid bilayers.…
The activation kinetics of the ion channels formed by colicin Ia incorporated into a planar bilayer lipid membrane (BLM) was investigated by the voltage clamp technique using different step voltage stimuli. The temporal behaviour of ion channels put in evidence a gain or a loss of memory, revealed by a specific sequence of electrical pulses used for stimulation.
A two-dimensional (2D) model is developed to describe the growth of spotty patterns (domains) in the lipid membranes which result from the coagulation of ion channels. It is assumed that the ion channels can coagulate when activated, e.g. the neurotransmitter may act as the surface-active substance for some ion channels in the lipid matrix or the activation may result in increase of polarity of the ion channels that give rise to their coagulation process due to the Brownian diffusive motion. The results show that the domain radius rD of the ion channels scales with time as rD~time^0.4.The slow…
It is known that lipid membranes become permeable in their melting regime. In microscopic conductance measurements on black lipid membranes one finds that conduction takes place via quantized events closely resembling those reported for protein ion channels. Here, we present data of ion currents through black lipid membranes in the presence and absence of the anesthetics octanol and ethanol, and compare them to a statistical thermodynamics model using parameters that are obtained from experimental calorimetric data. The conductance steps in pure lipid membrane suggest aqueous pores with the si…
Synthetic lipid membranes in the absence of proteins can display quantized conduction events for ions that are virtually indistinguishable from those of protein channel. By indistinguishable we mean that one cannot decide based on the current trace alone whether conductance events originate from a membrane, which does or does not contain channel proteins. Additional evidence is required to distinguish between the two cases, and it is not always certain that such evidence can be provided. The phenomenological similarities are striking and span a wide range of phenomena: The typical conductances…
We investigate the permeability of lipid membranes for fluorescence dyes and ions. We find that permeability reaches a maximum close to the chain melting transition of the membranes. Close to transitions, fluctuations in area and compressibility are high, leading to an increased likelihood of spontaneous lipid pore formation. Fluorescence Correlation Spectroscopy (FCS) reveals the permeability for rhodamine dyes across 100 nm vesicles. Using FCS, we find that the permeability of vesicle membranes for fluorescence dyes is within error proportional to the excess heat capacity. To estimate defect…
It is well known that at the gel-liquid phase transition temperature a lipid bilayer membrane exhibits an increased ion permeability. We analyze the quantized currents in which the increased permeability presents itself. The open time histogram shows a "-3/2" power law which implies an open-closed transition rate that decreases like $k(t) \propto t^{-1}$ as time evolves. We propose a "pore freezing" model to explain the observations. We discuss how this model also leads to the $1/f^α$ noise that is commonly observed in currents across biological and artificial membranes.
We investigate the possible influence of poly unsaturated fatty acids (PUFAs) in the lipid bilayer of cell membranes on the conduction properties of the selectivity filter of voltage gated ion channels. Any change of this conductivity can have major consequences on electrical signalling in brain and other cells. At the microscopic level a change in the concentration of PUFAs can cause a change in the pressure distribution within the lipid bilayer, and this in turn can lead to a change in the length of the selectivity filter. In order to estimate the consequences this might entail for the ion c…
The spatio-temporal organization of proteins and the associated morphological changes in membranes are of importance in cell signaling. Several mechanisms that promote the aggregation of proteins at low cell surface concentrations have been investigated in the past. We show, using Monte Carlo simulations, that the affinity of proteins for specific lipids can hasten its aggregation kinetics. The lipid membrane is modeled as a dynamically triangulated surface with the proteins defined as in-plane fields at the vertices. We show that, even at low protein concentrations, strong lipid-protein inter…
Monte Carlo (MC) Simulations, Differential Scanning Calorimetry (DSC) and Fourier Transform InfraRed (FTIR) spectroscopy were used to study the melting behavior of single lipid components in two-component membranes of 1,2-Dimyristoyl-D54-sn-Glycero-3-Phosphocholine (DMPC-d54) and 1,2-Distearoyl-sn-Glycero-3-Phosphocholine (DSPC). Microscopic information on the temperature dependent melting of the single lipid species could be investigated using FTIR. The microscopic behavior measured could be well described by the results from the MC simulations. These simulations also allowed to calculate hea…
Sound waves are excited on lipid monolayers using a set of planar electrodes aligned in parallel with the excitable medium. By measuring the frequency dependent change in the lateral pressure we are able to extract the sound velocity for the entire monolayer phase diagram. We demonstrate that this velocity can also be directly derived from the lipid monolayer compressibility and consequently displays a minimum in the phase transition regime. This minimum decreases from v0=170m/s for one component lipid monolayers down to vm=50m/s for lipid mixtures. No significant attenuation can be detected c…
Mechanoelectrical transduction in the inner ear is a biophysical process underlying the senses of hearing and balance. The key players involved in this process are mechanosensitive ion channels. They are located in the stereocilia of hair cells and opened by the tension in specialized molecular springs, the tip links, connecting adjacent stereocilia. When channels open, the tip links relax, reducing the hair-bundle stiffness. This gating compliance makes hair cells especially sensitive to small stimuli. The classical explanation for the gating compliance is that the conformational rearrangemen…
Microalgae have been shown as a potential bioresource for food, biofuel, and pharmaceutical products. During the growth phases with corresponding environmental conditions, microalgae accumulate different amounts of various metabolites. We quantified the lipid accumulation and analyzed swimming signatures (speed and trajectories) of the motile green alga, Dunaliella primolecta, during the lag-exponential-stationary growth cycle at different nutrient concentrations. We discovered significant changes in neutral lipid content and swimming signatures of microalgae across growth phases. The timing o…
Local changes in pH are known to significantly alter the state and activity of proteins and in particular enzymes. pH variations induced by pulses propagating along soft interfaces (e.g. the lipid bilayer) would therefore constitute an important pillar towards a new physical mechanism of biochemical regulation and biological signaling. Here we investigate the pH-induced physical perturbation of a lipid interface and the physiochemical nature of the subsequent acoustic propagation. Pulses are stimulated by local acidification of a lipid monolayer and propagate, in analogy to sound, at velocitie…
Ultra-long-chain fatty acids (ULCFAs) are biosynthesized in the restricted tissues such as retina, testis, and skin. The conformation of a single ULCFA, in which the sn-1 unsaturated chain has 32 carbons, in three types of tensionless phospholipid bilayers is studied by molecular dynamics simulations. It is found that the ultra-long tail of the ULCFA flips between two leaflets and fluctuates among an elongation into the opposite leaflet, lying between two leaflets, and turning back. As the number ratio of lipids in the opposite leaflet increases, the ratio of the elongated shape linearly decre…
Ultrasound is increasingly being used to modulate the properties of biological membranes for applications in drug delivery and neuromodulation. While various studies have investigated the mechanical aspect of the interaction such as acoustic absorption and membrane deformation, it is not clear how these effects transduce into biological functions, for example, changes in the permeability or the enzymatic activity of the membrane. A critical aspect of the activity of an enzyme is the thermal fluctuations of its solvation or hydration shell. Thermal fluctuations are also known to be directly rel…
The NV center in a diamond is a quantum sensor with exceptional quality for highly sensitive nanoscale analysis of NMR spectra and thermometry. In this study, we investigate nanoscale phase change detection of lipid bilayers utilizing ensemble-averaged nuclear spin detection from small volume ~ (6 nm)$^{3}$, which was determined by the depth of the NV center. Analysis of nanoscale NMR signal confirm thickness of lipid bilayer to be 6.2 nm $\pm$ 3.4 nm with proton density of 65 proton/nm$^{3}$ verifying formation of lipid bilayer on top of diamond sample. Correlation spectroscopy from nanoscale…
Biomembranes are thin capacitors with the unique feature of displaying phase transitions in a physiologically relevant regime. We investigate the voltage and lateral pressure dependence of their capacitance close to their chain melting transition. Since the gel and the fluid membrane have different area and thickness, the capacitance of the two membrane phases is different. In the presence of external fields, charges exert forces that can influence the state of the membrane, thereby influencing the transition temperature. This phenomenon is called electrostriction. We show that this effect all…
The soliton wave model of action potentials, and the proposal of induced lipid pores, are potentially paradigm shifting ideas which challenge accepted views of the Hodgkin-Huxley model and of protein-based ion channels. These two proposals are reviewed, and possible tests of each are presented. Also, three key non-electrical features seen during action potentials are reviewed; a shift in birefringence, the pattern of heat emission and absorption, and the expansion of cell diameter. How the soliton wave model uses the lipid phase transition to account for each of these three phenomena is contra…
In the proximity of melting transitions of artificial and biological membranes fluctuations in enthalpy, area, volume and concentration are enhanced. This results in domain formation, changes of the elastic constants, changes in permeability and slowing down of relaxation processes. In this study we used pressure perturbation calorimetry to investigate the relaxation time scale after a jump into the melting transition regime of artificial lipid membranes. This time corresponds to the characteristic rate of domain growth. The studies were performed on single-component large unilamellar and mult…
Genesis of a Horizontal Electric Field within the Lipid Bilayer: A Bilayer-Embedded Actuation Platform
Laboratory for Nanoelectronics and Spintronics, Research Institute of Electrical Communication (RIEC), Tohoku University（东北大学电气通信研究所纳米电子与自旋电子学实验室）；Graduate School of Biomedical Engineering, Tohoku University（东北大学生物医学工程学院研究生院）；School of Mechatronical Engineering, Beijing Institute of Technology（北京理工大学机电学院）；Advanced Institute for Materials Research (WPI-AIMR), Tohoku University（东北大学材料研究高等研究院）；Department of Molecular Neuroscience, Faculty of Medical Sciences, University of Fukui（福井大学医学科学部分子神经科学系）；Life Science Innovation Center, University of Fukui（福井大学生命科学创新中心）
Biomembranes, which are mainly composed of neutral and charged lipids, exhibit a large variety of functional structures and dynamics. Here, we report a coarse-grained molecular dynamics (MD) simulation of the phase separation and morphological dynamics in charged lipid bilayer vesicles. The screened long-range electrostatic repulsion among charged head groups delays or inhibits the lateral phase separation in charged vesicles compared with neutral vesicles, suggesting the transition of the phase-separation mechanism from spinodal decomposition to nucleation or homogeneous dispersion. Moreover,…
Cationic lipid membranes are known to form compact complexes with DNA and to be effective as gene delivery agents both in vitro and in vivo. Here we employ molecular dynamics simulations for a detailed atomistic study of lipid bilayers consisting of a mixture of cationic dimyristoyltrimethylammonium propane (DMTAP) and zwitterionic dimyristoylphosphatidylcholine (DMPC). Our main objective is to examine how the composition of the bilayers affects their structural and electrostatic properties in the liquid-crystalline phase. By varying the mole fraction of DMTAP, we have found that the area per …
Artificial bilayer lipid membranes (BLMs), along with patch-clamped membranes, are frequently used for functional analyses of membrane proteins. In both methods, the electric properties of membranes are characterized by only one parameter, namely, transmembrane potential. Here the construction of a novel BLM system was reported, in which membrane voltages can be controlled in a lateral direction in addition to conventional transmembrane direction. A microaperture was fabricated in a Teflon film and Ti electrodes were evaporated around the aperture. BLMs were reproducibly formed in the aperture…
Lipid bilayer membranes are the fundamental biological barriers that permit life. The bilayer dynamics largely participates in orchestrating cellular workings and is characterized by substantial stability together with extreme plasticity that allows controlled morphological/topological changes. Modeling and understanding the topological change of vesicle-like membrane at the scale of a full cell has proved an elusive aim. We propose and discuss here a continuum model able to encompass the fusion/fission transition of a bilayer membrane at the scale of a Large Unilamellar Vesicle and evaluate t…
As two-dimensional fluid shells, lipid bilayer membranes resist bending and stretching but are unable to sustain shear stresses. This property gives membranes the ability to adopt dramatic shape changes. In this paper, a finite element model is developed to study static equilibrium mechanics of membranes. In particular, a viscous regularization method is proposed to stabilize tangential mesh deformations and improve the convergence rate of nonlinear solvers. The Augmented Lagrangian method is used to enforce global constraints on area and volume during membrane deformations. As a validation of…
An action potential is typically described as a purely electrical change that propagates along the membrane of excitable cells. However, recent experiments have demonstrated that non-linear acoustic pulses that propagate along lipid interfaces and traverse the melting transition, share many similar properties with action potentials. Despite the striking experimental similarities, a comprehensive theoretical study of acoustic pulses in lipid systems is still lacking. Here we demonstrate that an idealized description of an interface near phase transition captures many properties of acoustic puls…
We study the effect of cholesterol on the structure of dipalmitoylphosphatidylcholine (DPPC) phospholipid bilayers. Using extensive molecular dynamics computer simulations at atomistic resolution we observe and quantify several structural changes upon increasing cholesterol content that are collectively known as the condensing effect: a thickening of the bilayer, an increase in lipid tail order, and a decrease in lateral area. We also observe a change in leaflet interdigitation and a lack thereof in the distributions of DPPC head group orientations. These results, obtained over a wide range of…
Simulating Curved Lipid Membranes Using Anchored Frozen Patches
Department of Materials Science and Engineering, Grainger College of Engineering, University of Illinois Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校格雷恩工程学院材料科学与工程系）
A biomimetic model of cell-cell communication was developed to probe the passive molecular transport across ion channels inserted in synthetic lipid bilayers formed between contacting droplets arranged in a linear array. Diffusion of a fluorescent probe across the array was measured for different pore concentrations. The diffusion characteristic time scale is found to vary non-linearly with the pore concentration. Our measurements are successfully modeled by a continuous time random walk description, whose waiting time is the first exit time from a droplet through a cluster of pores. The size …
Some biochemical and metabolic characteristics of bovine sperm cells irradiated with low-level laser were probed and correlated to the irradiation parameters. Bovine spermatozoa were exposed to spatially filtered light from a He-Ne laser (633 nm) with fluences from 150 to 600 mJ/cm2. General biochemical alterations were assessed by vibrational spectroscopy (micro-Fourier-Transform Infrared technique). The mitochondrial membrane potential was assessed by flow cytometry. Lipid peroxidation due to reactive oxygen species (ROS) production was assessed by thiobarbituric acid reactive substances (TB…
We monitored the action of phospholipase A2 (PLA2) on L- and D-dipalmitoylphosphatidylcholine (DPPC) Langmuir monolayers by mounting a Langmuir-trough on a wide-field fluorescence microscope with single molecule sensitivity. This made it possible to directly visualize the activity and diffusion behavior of single PLA2 molecules in a heterogeneous lipid environment during active hydrolysis. The experiments showed that enzyme molecules adsorbed and interacted almost exclusively with the fluid region of the DPPC monolayers. Domains of gel state L-DPPC were degraded exclusively from the gel-fluid …
For many biotechnological applications it would be useful to better understand the effects produced by electric fields on lipid membranes. This review discusses several aspects of the electrostatic properties of a planar lipid membrane with its surrounding electrolyte in a normal DC or AC electric field. In the planar geometry, the analysis of electrokinetic equations can be carried out quite far, allowing to characterize analytically the steady state and the dynamics of the charge accumulation in the Debye layers, which results from the application of the electric field. For a conductive memb…
Lipid bilayers composed of non-alpha hydroxy sphingosine ceramide (CER NS), cholesterol (CHOL), and free fatty acids (FFA), which are components of the human skin barrier, are studied via molecular dynamics simulations. Since mixtures of these lipids exist in dense gel phases with little molecular mobility at physiological conditions, care must be taken to ensure that the simulations become decorrelated from the initial conditions. Thus, we propose and validate an equilibration protocol based on simulated tempering in which the simulation takes a random walk through temperature space, allowing…
By reverting to spectroscopy, changes in the biological environment of a fluorescent probe can be monitored and the presence of various phases of the surrounding lipid bilayer membranes can be detected. This study highlights the important differences in orientation and location and therefore in efficiency between the probes when they are used in fluorescence microscopy to screen various lipid bilayer membrane phases. Dependent on the lipid composition, the angle between the transition state dipole moments of both probes and the normal to the membrane are found to deviate clearly from 90°. It i…
Magnetic field fluctuations arising from fundamental spins are ubiquitous in nanoscale biology, and are a rich source of information about the processes that generate them. However, the ability to detect the few spins involved without averaging over large ensembles has remained elusive. Here we demonstrate the detection of gadolinium spin labels in an artificial cell membrane under ambient conditions using a single-spin nanodiamond sensor. Changes in the spin relaxation time of the sensor located in the lipid bilayer were optically detected and found to be sensitive to near-individual proximal…
Membrane budding has been extensively studied as an equilibrium process attributed to the formation of coexisting domains or changes in the vesicle area to volume ratio (reduced volume). In contrast, non-equilibrium budding remains experimentally widely unexplored especially when time scales fall well below the characteristic diffusion time of lipidsτ . We show that localized mechanical perturbations, initiated by driving giant unilamellar vesicles (GUVs) through their lipid phase transition, leads to the immediate formation of rapidly growing, multiply localized, non-equilibrium buds, when th…
Neuroscience education can be promoted by the availability of low cost and engaging teaching materials. To address this issue, we developed an open-source lipid bilayer amplifier, the OpenPicoAmp, which is appropriate for use in introductory courses in biophysics or neurosciences dealing with the electrical properties of the cell membrane. The amplifier is designed using the common lithographic printed circuit board fabrication process and off-the-shelf electronic components. In addition, we propose a specific design for experimental chambers allowing the insertion of a commercially available …
Bilayer lipid membranes (BLMs) are an essential component of many biological systems, forming a functional barrier between the cell and the surrounding environment. When the membrane relaxes from a structural perturbation, the dynamics of the relaxation depends on the bilayer structure. We present a model of a BLM in a viscous solvent, including an explicit description of a 'thick' membrane, where the fluctuations in the thickness of a monolayer leaflet are coupled to changes in the lipid density within that monolayer. We find dispersion relations describing three intuitive forms of bilayer mo…
A method has been developed to monitor changes of the membrane potential across vesicle membranes in real time. Using the potential-sensitive fluorescent dye indocyanine and on the basis of water/lipid redistribution model, a calculation procedure has been introduced to estimate the membrane potential in vesicles with incorporated cytochrome-c oxidase. Physical parameters, such as vesicle size distribution and density of the lipid bilayer were estimated and used as calculation parameters. By extrapolation of transient potential change to zero time, the initial rate of the potential change (dU/…
Photothermal therapies are based on the optical excitation of plasmonic nanoparticles in the biological environment. The effects of the irradiation on the biological medium depend critically on the heat transfer process at the nanoparticle interface, on the temperature reached by the tissues as well as on the spatial extent of temperature gradients. Unfortunately, both the temperature and its biological effects are difficult to be probed experimentally at the molecular scale. Here, we approach this problem using nonequilibrium molecular dynamics simulations. We focus on photoporation, a photot…
Piezo ion channels underlie many forms of mechanosensation in vertebrates, and have been found to bend the membrane into strongly curved dome shapes. We develop here a methodology describing the self-assembly of lipids and Piezo into polyhedral bilayer vesicles. We validate this methodology for bilayer vesicles formed from bacterial mechanosensitive channels of small conductance, for which experiments found a polyhedral arrangement of proteins with snub cube symmetry and a well-defined characteristic vesicle size. On this basis, we calculate the self-assembly diagram for polyhedral bilayer ves…
Biological membranes constantly change their shape in response to external stimuli, and understanding the remodeling and stability of vesicles in heterogeneous environments is therefore of fundamental importance for a range of cellular processes. One crucial question is how vesicles respond to external osmotic stresses, imposed by differences in solute concentrations between the vesicle interior and exterior. Previous analyses of the membrane bending energy have predicted that micron-sized giant unilamellar vesicles (GUVs) should become globally deformed already for nanomolar concentration dif…
Supported Lipid Bilayers (SLBs) are model membranes formed at solid substrate surfaces. This architecture renders the membrane experimentally accessible to surface sensitive techniques used to study their properties, including Atomic Force Microscopy (AFM), optical fluorescence microscopy, Quartz Crystal Microbalance (QCM) and X-Ray/Neutron Reflectometry, and allows integration with technology for potential biotechnological applications such as drug screening devices. The experimental technique often dictates substrate choice or treatment, and it is anecdotally recognised that certain substrat…
Inspired by recent suggestions that the Alzheimer's amyloid beta peptide (A beta) can insert into cell membranes and form harmful ion channels, we model insertion of the 40 and 42 residue forms of the peptide into cell membranes using a Monte Carlo code which is specific at the amino acid level. We examine insertion of the regular A-beta peptide as well as mutants causing familial Alzheimer's disease, and find that all but one of the mutants change the insertion behavior by causing the peptide to spend more simulation steps in only one leaflet of the bilayer. We also find that A-beta 42, becau…
Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In particular, it has been recently recognized that ion channels assemble into surface nanoclusters in the soma of cultured neurons. However, the interactions of these molecules with surface nanodomains display a considerable degree of heterogeneity. Here, we investigate this heterogeneity and develop statistical tools based on the recurrence of individual trajectories to identify subpopulations within ion channels in the neuronal surface. We specifically study the dynamics of the K$^+$ channel Kv1.4 and the Na$^+$ …
In this paper we present the results of a large-scale numerical investigation of structural properties of a model of cell membrane, simulated as a bilayer of flexible molecules in vacuum. The study was performed by carrying out extensive Molecular Dynamics simulations, in the (NVE) micro-canonical ensemble, of two systems of different sizes (2x32 and 2x256 molecules), over a fairly large set of temperatures and densities, using parallel platforms and more standard serial computers. Depending on the dimension of the system, the dynamics was followed for physical times that go from few hundred o…
Clustering of ligand-binding receptors of different types on thickened isles of the cell membrane, namely lipid rafts, is an experimentally observed phenomenon. Although its influence on cell response is deeply investigated, the role of the coupling between mechanical processes and multiphysics involving the active receptors and the surrounding lipid membrane during ligand-binding has not yet been understood. Specifically, the focus of this work is on G-protein-coupled receptors (GPCRs), which regulate specific cell processes through chemical signalling pathways involving a synergistic balance…
