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1.
Sci Rep ; 12(1): 7160, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35504939

RESUMO

Membrane lungs consist of thousands of hollow fiber membranes packed together as a bundle. The devices often suffer from complications because of non-uniform flow through the membrane bundle, including regions of both excessively high flow and stagnant flow. Here, we present a proof-of-concept design for a membrane lung containing a membrane module based on triply periodic minimal surfaces (TPMS). By warping the original TPMS geometries, the local permeability within any region of the module could be raised or lowered, allowing for the tailoring of the blood flow distribution through the device. By creating an iterative optimization scheme for determining the distribution of streamwise permeability inside a computational porous domain, the desired form of a lattice of TPMS elements was determined via simulation. This desired form was translated into a computer-aided design (CAD) model for a prototype device. The device was then produced via additive manufacturing in order to test the novel design against an industry-standard predicate device. Flow distribution was verifiably homogenized and residence time reduced, promising a more efficient performance and increased resistance to thrombosis. This work shows the promising extent to which TPMS can serve as a new building block for exchange processes in medical devices.


Assuntos
Pulmão , Simulação por Computador , Membranas , Permeabilidade , Porosidade
2.
Sci Rep ; 12(1): 7676, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538113

RESUMO

BAR (Bin/Amphiphysin/Rvs) domain containing proteins function as lipid bilayer benders and curvature sensors, and they contribute to membrane shaping involved in cell signaling and metabolism. The mechanism for their membrane shape sensing has been investigated by both equilibrium binding and kinetic studies. In prior research, stopped-flow spectroscopy has been used to deduce a positive dependence on membrane curvature for the binding rate constant, kon, of a BAR protein called endophilin. However, the impact of bulk diffusion of endophilin, on the kinetic binding parameters has not been thoroughly considered. Employing similar methods, and using lipid vesicles of multiple sizes, we obtained a linear dependence of kon on vesicle curvature. However, we found that the observed relation can be explained without considering the local curvature sensing ability of endophilin in the membrane association process. In contrast, the diffusion-independent unbinding rate constant (koff) obtained from stopped-flow measurements shows a negative dependence on membrane curvature, which is controlled/mediated by endophilin-membrane interactions. This latter dependency, in addition to protein-protein interactions on the membrane, explains the selective binding of BAR proteins to highly curved membranes in equilibrium binding experiments.


Assuntos
Aciltransferases , Bicamadas Lipídicas , Aciltransferases/metabolismo , Membrana Celular/metabolismo , Cinética , Bicamadas Lipídicas/química , Membranas/metabolismo
3.
Nat Commun ; 13(1): 2174, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449207

RESUMO

Endosomal Sorting Complex Required for Transport III (ESCRT-III) is a conserved protein system involved in many cellular processes resulting in membrane deformation and scission, topologically away from the cytoplasm. However, little is known about the transition of the planar membrane-associated protein assembly into a 3D structure. High-speed atomic force microscopy (HS-AFM) provided insights into assembly, structural dynamics and turnover of Snf7, the major ESCRT-III component, on planar supported lipid bilayers. Here, we develop HS-AFM experiments that remove the constraints of membrane planarity, crowdedness, and support rigidity. On non-planar membranes, Snf7 monomers are curvature insensitive, but Snf7-spirals selectively adapt their conformation to membrane geometry. In a non-crowded system, Snf7-spirals reach a critical radius, and remodel to minimize internal stress. On non-rigid supports, Snf7-spirals compact and buckle, deforming the underlying bilayer. These experiments provide direct evidence that Snf7 is sufficient to mediate topological transitions, in agreement with the loaded spiral spring model.


Assuntos
Complexos Endossomais de Distribuição Requeridos para Transporte , Bicamadas Lipídicas , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Bicamadas Lipídicas/química , Membranas/metabolismo , Microscopia de Força Atômica
4.
Environ Sci Technol ; 56(9): 5775-5785, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35465657

RESUMO

Despite increasing sustainable water purification, current desalination membranes still suffer from insufficient permeability and treatment efficiency, greatly hindering extensive practical applications. In this work, we provide a new membrane design protocol and molecule-level mechanistic understanding of vapor transport for the treatment of hypersaline waters via a membrane distillation process by rationally fabricating more robust metal-based carbon nanotube (CNT) network membranes, featuring a superhydrophobic superporous surface (80.0 ± 2.3% surface porosity). With highly permeable ductile metal hollow fibers as substrates, the construction of a superhydrophobic (water contact angle ∼170°) CNT network layer endows the membranes with not only almost perfect salt rejection (over 99.9%) but a promising water flux (43.6 L·m-2·h-1), which outperforms most existing inorganic distillation membranes. Both experimental and molecular dynamics simulation results indicate that such an enhanced water flux can be ascribed to an ultra-low liquid-solid contact interface (∼3.23%), allowing water vapor to rapidly transport across the membrane structure via a combined mechanism of Knudsen diffusion (more dominant) and viscous flow while efficiently repelling high-salinity feed via forming a Cassie-Baxter state. A more hydrophobic surface is more in favor of not only water desorption from the CNT outer surface but superfast and frictionless water vapor transport. By constructing a new superhydrophobic triple-phase interface, the conceptional design strategy proposed in this work can be expected to be extended to other membrane material systems as well as more water treatment applications.


Assuntos
Nanotubos de Carbono , Purificação da Água , Destilação , Gases , Membranas , Vapor
5.
Soft Matter ; 18(17): 3384-3394, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35416229

RESUMO

Bin/Amphiphysin/Rvs superfamily proteins and other curvature-inducing proteins have anisotropic shapes and anisotropically bend biomembranes. Here, we report how the anisotropic proteins bind the membrane tube and are orientationally ordered using mean-field theory including an orientation-dependent excluded volume. The proteins exhibit a second-order or first-order nematic transition with increasing protein density depending on the radius of the membrane tube. The tube curvatures for the maximum protein binding and orientational order are different and varied by the protein density and rigidity. As the external force along the tube axis increases, a first-order transition from a large tube radius with low protein density to a small radius with high density occurs once, and subsequently, the protein orientation tilts to the tube-axis direction. When an isotropic bending energy is used for the proteins with an elliptic shape, the force-dependence curves become symmetric and the first-order transition occurs twice. This theory quantitatively reproduces the results of meshless membrane simulation for short proteins, whereas deviations are seen for long proteins owing to the formation of protein clusters.


Assuntos
Anisotropia , Membrana Celular/metabolismo , Simulação por Computador , Membranas , Ligação Proteica
6.
Langmuir ; 38(18): 5752-5758, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35476922

RESUMO

The question of how peptide chain aggregation is influenced by lipid membranes with varying shapes and structures is crucial for a detailed understanding of the neurotoxicity effect of the peptide chains. Not like the more usual spherical liposomes and planar lipid membranes, herein, we use lipid nanotubules as a model of important neuron synapse nanowire structures and devote particular attention to the effect of nanotubule fluidity on amyloid-ß peptide (Aß) chain aggregation. We apply single-molecule tracking (SMT) to elucidate how Aß chains diffuse and aggregate on lipid nanotubules with different fluidities. The physical mechanism implies that fluidic lipid nanotubules facilitate the super-diffusion of two-dimensional (2D)-mobile precursor Aß chains and promote their aggregation. This aggregation mechanism is retarded on less fluidic lipid nanotubules where the super-diffusion of 2D-mobile precursor Aß chains is restricted by "frozen" lipids with less mobility. This work provides a mechanistic explanation for Aß chain aggregation on fluidic lipid nanotubules.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Peptídeos beta-Amiloides/química , Difusão , Humanos , Lipídeos , Lipossomos/química , Membranas , Fragmentos de Peptídeos
7.
J Vis Exp ; (182)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35467657

RESUMO

In the human body, most of the major physiologic reactions involved in the immune response and blood coagulation proceed on the membranes of cells. An important first step in any membrane-dependent reaction is binding of protein on the phospholipid membrane. An approach to studying protein interaction with lipid membranes has been developed using fluorescently labeled proteins and flow cytometry. This method allows the study of protein-membrane interactions using live cells and natural or artificial phospholipid vesicles. The advantage of this method is the simplicity and availability of reagents and equipment. In this method, proteins are labeled using fluorescent dyes. However, both self-made and commercially available, fluorescently labeled proteins can be used. After conjugation with a fluorescent dye, the proteins are incubated with a source of the phospholipid membrane (microvesicles or cells), and the samples are analyzed by flow cytometry. The obtained data can be used to calculate the kinetic constants and equilibrium Kd. In addition, it is possible to estimate the approximate number of protein binding sites on the phospholipid membrane using special calibration beads.


Assuntos
Micropartículas Derivadas de Células , Fosfolipídeos , Micropartículas Derivadas de Células/metabolismo , Citometria de Fluxo/métodos , Corantes Fluorescentes/química , Humanos , Membranas/metabolismo , Fosfolipídeos/química
8.
Int J Mol Sci ; 23(7)2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35409329

RESUMO

Although the pharmacological activity of capsaicin has been explained by its specific binding to transient receptor potential vanilloid type 1, the amphiphilic structure of capsaicin may enable it to act on lipid bilayers. From a mechanistic point of view, we investigated whether capsaicin and its antagonist capsazepine interact with biomimetic membranes, and how capsazepine influences the membrane effect of capsaicin. Liposomal phospholipid membranes and neuro-mimetic membranes were prepared with 1,2-dipalmitoylphosphatidylcholine and with 1-palmitoyl-2-oleoylphosphatidylcholine and sphingomyelin plus cholesterol, respectively. These membrane preparations were subjected to reactions with capsaicin and capsazepine at 0.5-250 µM, followed by measuring fluorescence polarization to determine the membrane interactivity to modify the fluidity of membranes. Both compounds acted on 1,2-dipalmitoylphosphatidylcholine bilayers and changed membrane fluidity. Capsaicin concentration-dependently interacted with neuro-mimetic membranes to increase their fluidity at low micromolar concentrations, whereas capsazepine inversely decreased the membrane fluidity. When used in combination, capsazepine inhibited the effect of capsaicin on neuro-mimetic membranes. In addition to the direct action on transmembrane ion channels, capsaicin and capsazepine share membrane interactivity, but capsazepine is likely to competitively antagonize capsaicin's interaction with neuro-mimetic membranes at pharmacokinetically-relevant concentrations. The structure-specific membrane interactivity may be partly responsible for the analgesic effect of capsaicin.


Assuntos
1,2-Dipalmitoilfosfatidilcolina , Capsaicina , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Bicamadas Lipídicas/química , Membranas/metabolismo
9.
Langmuir ; 38(18): 5674-5681, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35471971

RESUMO

We compare the fusion of giant lipid and block-copolymer vesicles on glass and poly(dimethylsiloxane) substrates. Both types of vesicles are similar in their ability to fuse to hydrophilic substrates and form patches with distinct heart or circular shapes. We use epifluorescence/confocal microscopy and atomic force microscopy on membrane patches to (i) characterize bilayer fluidity and patch-edge stability and (ii) follow the intermediate stages in the formation of continuous supported bilayers. Polymer membranes show much lower membrane fluidity and, unlike lipids, an inability of adjacent patches to fuse spontaneously into continuous membranes. We ascribe this effect to hydration repulsion forces acting between the patch edges, which can be diminished by increasing the sample temperature. We show that large areas of supported polymer membranes can be created by fusing giant vesicles on glass or poly(dimethylsiloxane) substrates and annealing their edges.


Assuntos
Bicamadas Lipídicas , Polímeros , Bicamadas Lipídicas/química , Fluidez de Membrana , Fusão de Membrana , Membranas , Polímeros/química
10.
J Cell Sci ; 135(7)2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35388894

RESUMO

Dopey family proteins play crucial roles in diverse processes from morphogenesis to neural function and are conserved from yeast to mammals. Understanding the mechanisms behind these critical functions could have major clinical significance, as dysregulation of Dopey proteins has been linked to the cognitive defects in Down syndrome, as well as neurological diseases. Dopey proteins form a complex with the non-essential GEF-like protein Mon2 and an essential lipid flippase from the P4-ATPase family. Different combinations of Dopey, Mon2 and flippases have been linked to regulating membrane remodeling, from endosomal recycling to extracellular vesicle formation, through their interactions with lipids and other membrane trafficking regulators, such as ARL1, SNX3 and the kinesin-1 light chain KLC2. Despite these important functions and their likely clinical significance, Dopey proteins remain understudied and their roles elusive. Here, we review the major scientific discoveries relating to Dopey proteins and detail key open questions regarding their function to draw attention to these fascinating enigmas.


Assuntos
Proteínas Monoméricas de Ligação ao GTP , Proteínas de Saccharomyces cerevisiae , Adenosina Trifosfatases/metabolismo , Animais , Endossomos/metabolismo , Mamíferos/metabolismo , Membranas/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
11.
Biomacromolecules ; 23(4): 1505-1518, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35266692

RESUMO

The desire to develop artificial cells to imitate living cells in synthetic vesicle platforms has continuously increased over the past few decades. In particular, heterogeneous synthetic vesicles made from two or more building blocks have attracted attention for artificial cell applications based on their multifunctional modules with asymmetric structures. In addition to the traditional liposomes or polymersomes, polypeptides and proteins have recently been highlighted as potential building blocks to construct artificial cells owing to their specific biological functionalities. Incorporating one or more functionally folded, globular protein into synthetic vesicles enables more cell-like functions mediated by proteins. This Review highlights the recent research about synthetic vesicles toward artificial cell models, from traditional synthetic vesicles to protein-assembled vesicles with asymmetric structures. We aim to provide fundamental and practical insights into applying knowledge on molecular self-assembly to the bottom-up construction of artificial cell platforms with heterogeneous building blocks.


Assuntos
Células Artificiais , Lipossomos , Membranas , Membranas Artificiais , Peptídeos
12.
J Cell Sci ; 135(5)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35267021

RESUMO

At organelle-organelle contact sites, proteins have long been known to facilitate the rapid movement of lipids. Classically, this lipid transport involves the extraction of single lipids into a hydrophobic pocket on a lipid transport protein. Recently, a new class of lipid transporter has been described with physical characteristics that suggest these proteins are likely to function differently. They possess long hydrophobic tracts that can bind many lipids at once and physically span the entire gulf between membranes at contact sites, suggesting that they may act as bridges to facilitate bulk lipid flow. Here, we review what has been learned regarding the structure and function of this class of lipid transporters, whose best characterized members are VPS13 and ATG2 proteins, and their apparent coordination with other lipid-mobilizing proteins on organelle membranes. We also discuss the prevailing hypothesis in the field, that this type of lipid transport may facilitate membrane expansion through the bulk delivery of lipids, as well as other emerging hypotheses and questions surrounding these novel lipid transport proteins.


Assuntos
Membranas Mitocondriais , Biogênese de Organelas , Proteínas de Transporte/metabolismo , Lipídeos , Membranas/metabolismo , Membranas Mitocondriais/metabolismo , Proteínas/metabolismo
13.
J Phys Chem B ; 126(13): 2507-2512, 2022 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-35349297

RESUMO

A Landau theory is constructed for the gel/fluid transition of a lipid bilayer wrapped around a spherical nanoparticle (lipid-wrapped nanoparticle, LNP). The bilayer is regarded as a regular solution of gel and fluid lipids with distinct inter- and intralayer interactions plus the interaction of the core with the inner layer. It is required that both the inner and the outer surfaces of the bilayer are perfectly covered with lipids, with the gel and fluid lipids having different areas/lipid. The equilibrium state is found by minimizing the free energy as a function of the fractions of fluid lipids in the inner and outer layers. The transition has been studied extensively for lamellar membranes in the thermodynamic limit. LNP have significant curvature and are not in the thermodynamic limit. The increase of the gel energy with curvature, identified in our previous work as its most important effect, is included. The focus of the paper is the dependence of the transition on the core radius, R, controlling curvature, and the core-lipid interaction. With decreasing R, trends found in experiment are reproduced in a model calculation: (1) decrease of the transition temperature, Tm, (2) decoupling of the transitions in the inner and outer layers, and (3) possibility of lower Tm in the inner layer. The disruption of gel packing by curvature and the interaction of the core with the inner layer are highlighted as the most important determinants of deviation from bulk behavior.


Assuntos
Bicamadas Lipídicas , Nanopartículas , Membranas , Transição de Fase , Termodinâmica
14.
Cell Rep ; 38(9): 110445, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35235791

RESUMO

TACAN is an ion channel-like protein that may be involved in sensing mechanical pain. Here, we present the cryo-electron microscopic structure of human TACAN (hTACAN). hTACAN forms a dimer in which each protomer consists of a transmembrane globular domain (TMD) containing six helices and an intracellular domain (ICD) containing two helices. Molecular dynamic simulations suggest that each protomer contains a putative ion conduction pore. A single-point mutation of the key residue Met207 greatly increases membrane pressure-activated currents. In addition, each hTACAN subunit binds one cholesterol molecule. Our data show the molecular assembly of hTACAN and suggest that wild-type hTACAN is in a closed state.


Assuntos
Proteínas de Transporte , Canais Iônicos/química , Dor , Microscopia Crioeletrônica , Humanos , Membranas , Domínios Proteicos , Subunidades Proteicas
15.
Langmuir ; 38(11): 3522-3529, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35263105

RESUMO

Ceramide is a sphingolipid that constitutes only a small fraction of membrane biomolecules but plays a central role in regulating many biological processes. The ceramide level in cell membranes can drastically increase in response to external damage, which has been hypothesized to involve ceramide's biophysical role that increases the membrane packing density and lowers the membrane permeability. However, direct observation of the consequent influence on membrane chemistry resulting from these ceramide-induced physical properties has been absent. Using our unique field-induced droplet ionization mass spectrometry technique combined with molecular dynamics simulations, here we report that the addition of ceramide to POPC monolayer membranes at the air-water interface greatly reduces the chemical damage from potent chemicals, •OH radicals, and HCl vapor, by stiffening the membrane packing and lowering the permeability. These results shed new light on the underlying chemoprotective role of ceramide in lipid membranes, which might serve as a previously unknown protection mechanism in response to external stimuli that cause cell stress or death.


Assuntos
Ceramidas , Bicamadas Lipídicas , Membrana Celular/química , Ceramidas/química , Bicamadas Lipídicas/química , Membranas/metabolismo , Simulação de Dinâmica Molecular
16.
Langmuir ; 38(11): 3412-3421, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35263113

RESUMO

Amphiphilic imidazolium-based ionic liquids (ILs) have proven their efficacy in altering the membrane integrity and dynamics. The present article investigates the phase-separated domains in a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membrane induced by 1,3 dialkylated imidazolium IL. Isotherm measurements on DPPC monolayers formed at the air-water interface have shown a decrease in the mean molecular area with the addition of this IL. The positive value of the excess Gibbs free energy of mixing indicates an unfavorable mixing of the IL into the lipid. This leads to IL-induced phase-separated domains in the multilayer of the lipid confirmed by the occurrence of two sets of equidistance peaks in the X-ray reflectivity data. The electron density profile along the surface normal obtained by the swelling method shows the bilayer thickness of the newly formed IL-rich phase to be substantially lower (∼34 Å) than the DPPC phase (∼45.8 Å). This IL-rich phase has been confirmed to be interdigitated, showing an enhanced electron density in the tail region due to the overlapping hydrocarbon chains. Differential scanning calorimetry measurements showed that the incorporation of IL enhances the fluidity of the lipid bilayer. Therefore, the study indicates the formation of an interdigitated phase with a lower order compared to the gel phase in the DPPC membrane supplemented with the IL.


Assuntos
Líquidos Iônicos , 1,2-Dipalmitoilfosfatidilcolina/química , Varredura Diferencial de Calorimetria , Líquidos Iônicos/química , Bicamadas Lipídicas/química , Membranas , Fosfolipídeos/química
17.
Viruses ; 14(3)2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35337029

RESUMO

HIV-1 viral particle assembly occurs specifically at the plasma membrane and is driven primarily by the viral polyprotein Gag. Selective association of Gag with the plasma membrane is a key step in the viral assembly pathway, which is traditionally attributed to the MA domain. MA regulates specific plasma membrane binding through two primary mechanisms including: (1) specific interaction of the MA highly basic region (HBR) with the plasma membrane phospholipid phosphatidylinositol (4,5) bisphosphate [PI(4,5)P2], and (2) tRNA binding to the MA HBR, which prevents Gag association with non-PI(4,5)P2 containing membranes. Gag multimerization, driven by both CA-CA inter-protein interactions and NC-RNA binding, also plays an essential role in viral particle assembly, mediating the establishment and growth of the immature Gag lattice on the plasma membrane. In addition to these functions, the multimerization of HIV-1 Gag has also been demonstrated to enhance its membrane binding activity through the MA domain. This review provides an overview of the mechanisms regulating Gag membrane binding through the MA domain and multimerization through the CA and NC domains, and examines how these two functions are intertwined, allowing for multimerization mediated enhancement of Gag membrane binding.


Assuntos
HIV-1 , Membrana Celular/metabolismo , HIV-1/genética , Membranas/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Ligação Proteica , Montagem de Vírus , Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
19.
Int J Implant Dent ; 8(1): 9, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35243561

RESUMO

BACKGROUND: The purpose of this study was to evaluate the effects of resorbable membranes, combined with a shape memory alloy (SMA) mesh device, on bone formation using a timed-release system for periosteal expansion osteogenesis (TIME-PEO). MATERIALS AND METHODS: Twelve Japanese white rabbits were used in this study. An SMA device was inserted under the forehead periosteum, pushed and bent for attachment to the bone surface, and then fixed using resorbable thread. The rabbits were divided into four groups: C1 (5 weeks postoperatively without membrane), C2 (8 weeks postoperatively without membrane), E1 (5 weeks postoperatively with membrane), and E2 (8 weeks postoperatively with membrane). The rabbits were killed 5 or 8 weeks after the operation and the newly formed bone was assessed histologically and radiographically. RESULTS: SMA devices, concealed under soft tissue until the time of euthanasia, did not cause active inflammation. The mean activation height, from the original bone surface to the midpoint of the mesh, was 3.1 ± 0.6 mm. Newly formed bone was observed, and most of the subperiosteal space underneath the device was occupied by fibrous tissue. Immature bone was present at the outer surface of the original skull bone in all groups. On histomorphometric analysis, there was no significant difference in the volume of the new bone between C1 and E1 (p = 0.885), and C2 and E2 (p = 0.545). CONCLUSIONS: PEO using an SMA mesh device, which is based on guided bone regeneration (in atrophic alveolar bone), shows promise as an alternative for bone augmentation, irrespective of whether a resorbable membrane is used.


Assuntos
Lagomorpha , Osteogênese , Animais , Regeneração Óssea , Colágeno/farmacologia , Membranas , Coelhos , Ligas de Memória da Forma , Crânio/diagnóstico por imagem
20.
Methods Mol Biol ; 2405: 115-136, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35298811

RESUMO

Understanding the interactions between peptides and lipid membranes could not only accelerate the development of antimicrobial peptides as treatments for infections but also be applied to finding targeted therapies for cancer and other diseases. However, designing biophysical experiments to study molecular interactions between flexible peptides and fluidic lipid membranes has been an ongoing challenge. Recently, with hardware advances, algorithm improvements, and more accurate parameterizations (i.e., force fields), all-atom molecular dynamics (MD) simulations have been used as a "computational microscope" to investigate the molecular interactions and mechanisms of membrane-active peptides in cell membranes (Chen et al., Curr Opin Struct Biol 61:160-166, 2020; Ulmschneider and Ulmschneider, Acc Chem Res 51(5):1106-1116, 2018; Dror et al., Annu Rev Biophys 41:429-452, 2012). In this chapter, we describe how to utilize MD simulations to predict and study peptide dynamics and how to validate the simulations by circular dichroism, intrinsic fluorescent probe, membrane leakage assay, electrical impedance, and isothermal titration calorimetry. Experimentally validated MD simulations open a new route towards peptide design starting from sequence and structure and leading to desirable functions.


Assuntos
Simulação de Dinâmica Molecular , Peptídeos , Membrana Celular/metabolismo , Lipídeos/análise , Membranas , Peptídeos/metabolismo
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