Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 19.180
Filtrar
1.
Dev Cell ; 58(1): 18-33.e6, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36626869

RESUMO

Actin-based protrusions extend from the surface of all eukaryotic cells, where they support diverse activities essential for life. Models of protrusion growth hypothesize that actin filament assembly exerts force for pushing the plasma membrane outward. However, membrane-associated myosin motors are also abundant in protrusions, although their potential for contributing, growth-promoting force remains unexplored. Using an inducible system that docks myosin motor domains to membrane-binding modules with temporal control, we found that application of myosin-generated force to the membrane is sufficient for driving robust protrusion elongation in human, mouse, and pig cell culture models. Protrusion growth scaled with motor accumulation, required barbed-end-directed force, and was independent of cargo delivery or recruitment of canonical elongation factors. Application of growth-promoting force was also supported by structurally distinct myosin motors and membrane-binding modules. Thus, myosin-generated force can drive protrusion growth, and this mechanism is likely active in diverse biological contexts.


Assuntos
Actinas , Miosinas , Camundongos , Animais , Humanos , Suínos , Miosinas/metabolismo , Actinas/metabolismo , Citoesqueleto de Actina/metabolismo , Membrana Celular/metabolismo , Membranas/metabolismo
2.
Phys Rev Lett ; 130(1): 011402, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36669226

RESUMO

We show that a generic relativistic membrane with in-plane pressure and surface density having the same sign is unstable with respect to a series of warping mode instabilities with high wave numbers. We also examine the criteria of instability for commonly studied exotic compact objects with membranes, such as gravastars, anti-de Sitter bubbles, and thin-shell wormholes. For example, a gravastar which satisfies the weak energy condition turns out to be dynamically unstable. A thin-layer black hole mimicker is stable only if it has positive pressure and negative surface density (such as a wormhole), or vice versa.


Assuntos
Membranas , Simulação de Dinâmica Molecular
3.
Anal Chem ; 95(4): 2513-2522, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36683262

RESUMO

Cell membrane transport is the first and crucial step for bioprobes to realize the diagnosis, imaging, and therapy in cells. However, during this transport, there is a trade-off between anchoring and internalization steps, which will seriously affect the membrane transport efficiency. In the past, because the interaction between probes and cell membrane is constant, this challenge is hard to solve. Here, we proposed a strategy to regulate the membrane affinity of multi-module probes that enabled probe to have strong affinity during cell membrane anchoring and weak affinity during internalization. Specifically, a multi-module probe defined as LK-M-NA was constructed, which consisted of three main parts, membrane-anchoring α-helix peptide (LK), anchoring regulator (M), and therapeutic module (NA). With the α-helix module, LK-M-NA was able to rapidly anchor on the cell membrane and the binding energy was -1450.90 kcal/mol. However, after pericellular cleavage by the highly active matrix metalloproteinase-2 , LK could be removed due to the breakage of M and the binding energy reduced to -869.95 kcal/mol. Thus, the internalization restriction caused by high affinity was relieved. Owing to the alterable affinity, the membrane transport efficiency of LK-M-NA increased to 14.58%, well addressing the trade-off problem.


Assuntos
Metaloproteinase 2 da Matriz , Peptídeos , Membrana Celular , Transporte Biológico , Membranas
4.
Langmuir ; 39(1): 295-307, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36534123

RESUMO

We report the influence of membrane composition on the multiscale remodeling of multicomponent lipid bilayers initiated by contact with the amphiphilic bacterial quorum sensing signal N-(3-oxo)-dodecanoyl-l-homoserine lactone (3-oxo-C12-AHL) and its anionic headgroup hydrolysis product, 3-oxo-C12-HS. We used fluorescence microscopy and quartz crystal microbalance with dissipation (QCM-D) to characterize membrane reformation that occurs when these amphiphiles are placed in contact with supported lipid bilayers (SLBs) composed of (i) 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) containing varying amounts of cholesterol or (ii) mixtures of DOPC and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE, a conical zwitterionic lipid) or 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS, a model anionic lipid). In general, we observe these mixed-lipid membranes to undergo remodeling events, including the formation and subsequent collapse of long tubules and the formation of hemispherical caps, upon introduction to biologically relevant concentrations of 3-oxo-C12-AHL and 3-oxo-C12-HS in ways that differ substantially from those observed in single-component DOPC membranes. These differences in bilayer reformation and their associated dynamics can be understood in terms of the influence of membrane composition on the time scales of molecular flip-flop, lipid packing defects, and lipid phase segregation in these materials. The lipid components investigated here are representative of classes of lipids that comprise both naturally occurring cell membranes and many useful synthetic soft materials. These studies thus represent a first step toward understanding the ways in which membrane composition can impact interactions with this important class of bacterial signaling molecules.


Assuntos
Bicamadas Lipídicas , Percepção de Quorum , Bicamadas Lipídicas/química , Membrana Celular/metabolismo , Membranas/metabolismo , Microscopia de Fluorescência , Fosfatidilcolinas/química
5.
ACS Macro Lett ; 12(1): 8-13, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36521059

RESUMO

Block copolymers have attracted recent interest as candidate materials for ultrafiltration membranes, due to their ability to form isoporous integral-asymmetric membranes by the combined processes of self-assembly and nonsolvent-induced phase separation (SNIPS). However, the dependence of surface layer and substructure morphologies on the processing variables associated with SNIPS is not well understood nor is the interplay between microphase and macrophase separation in block copolymers undergoing such coagulation. Here, we use dynamical self-consistent field theory to simulate the microstructure evolution of block copolymer films during SNIPS and find that such films form the desired sponge-like asymmetric porous substructure only if the solvent and nonsolvent have opposite block selectivities and that otherwise they form a dense nonporous microphase-separated film. Our results could have important implications for the choices of solvent and nonsolvent in the processing of block copolymer membranes.


Assuntos
Membranas Artificiais , Polímeros , Polímeros/química , Solventes/química , Membranas , Porosidade
6.
Nano Lett ; 23(1): 107-115, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36541945

RESUMO

In comparison to the well-developed proton-exchange-membrane fuel cells, anion-exchange-membrane fuel cells (AEMFCs) permit adoption of platinum-group-metal (PGM)-free catalysts due to the alkaline environment, giving a substantial cost reduction. However, previous AEMFCs have generally shown unsatisfactory performances due to the lack of effective PGM-free catalysts that can endure harsh fuel cell conditions. Here we report a plasma-assisted synthesis of high-quality nickel nitride (Ni3N) and zirconium nitride (ZrN) employing dinitrogen as the nitrogen resource, exhibiting exceptional catalytic performances toward hydrogen oxidation and oxygen reduction in an alkaline enviroment, respectively. A PGM-free AEMFC assembled by using Ni3N as the anode and ZrN as the cathode delivers power densities of 256 mW cm-2 under an H2-O2 condition and 151 mW cm-2 under an H2-air condition. Furthermore, the fuel cell shows no evidence of degradation after 25 h of operation. This work creates opportunities for developing high-performance and durable AEMFCs based on metal nitrides.


Assuntos
Níquel , Platina , Membranas , Membrana Celular , Ânions , Prótons
7.
Methods Mol Biol ; 2613: 215-227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587082

RESUMO

Gangliosides play a variety of physiological roles and are one of the most important lipid raft constituents. However, their dynamic behaviors have scarcely been investigated in living cells because of the lack of fluorescent probes that behave like their parental molecules. Recently, fluorescent ganglioside probes that mimic native ganglioside behaviors have been developed. In this chapter, I discuss the recent advances in research related to the lateral localization and dynamic behaviors of gangliosides in the plasma membranes of living cells.


Assuntos
Gangliosídeos , Imagem Individual de Molécula , Gangliosídeos/metabolismo , Membrana Celular/metabolismo , Membranas/metabolismo , Nanotecnologia
8.
J Cell Biol ; 222(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36547519

RESUMO

Disruptions in membrane trafficking are associated with neurodevelopmental disorders, but underlying pathological mechanisms remain largely unknown. In this issue, O'Brien et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202112108) show how GARP regulates sterol transfer critical for remodeling of dendrites in flies.


Assuntos
Dendritos , Proteínas de Membrana , Transtornos do Neurodesenvolvimento , Esteróis , Dendritos/patologia , Membranas , Transtornos do Neurodesenvolvimento/fisiopatologia , Esteróis/metabolismo , Proteínas de Membrana/metabolismo
10.
Phys Chem Chem Phys ; 25(5): 3639-3650, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36541682

RESUMO

LL-III is an anticancer peptide and has the ability to translocate across tumor cell membranes, which indicates that its action mechanism could be non-membranolytic. However, the exact mechanism through which the peptide gains access into the cell cytoplasm is still unknown. Here, we use a plethora of physico-chemical techniques to characterize the interaction of LL-III with liposomes mimicking the lipid matrix of the tumor cell membrane and its effect on the microstructure and thermotropic properties of the membrane. Furthermore, the effect of the presence of Ca2+ cations at physiological concentration was also investigated. For comparison, the interaction of LL-III with liposomes mimicking the normal cell membrane was also studied. Our results show that the peptide selectively interacts with the model tumor cell membrane. This interaction does not disrupt the lipid bilayer but deeply alters its properties by promoting lipid lateral reorganization and increasing membrane permeability. Overall, our data provide a molecular level description of the interaction of the peptide with the model tumor membrane and are fully consistent with the non-membranolytic action mechanism.


Assuntos
Bicamadas Lipídicas , Lipossomos , Bicamadas Lipídicas/química , Lipossomos/química , Membrana Celular/química , Peptídeos/química , Membranas
11.
Langmuir ; 39(1): 1-11, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36576966

RESUMO

Membrane-enveloped viruses are responsible for most viral pandemics in history, and more effort is needed to advance broadly applicable countermeasures to mitigate the impact of future outbreaks. In this Perspective, we discuss how biosensing techniques associated with lipid model membrane platforms are contributing to improving our mechanistic knowledge of membrane fusion and destabilization that is closely linked to viral entry as well as vaccine and antiviral drug development. A key benefit of these platforms is the simplicity of interpreting the results which can be complemented by other techniques to decipher more complicated biological observations and evaluate the biophysical functionalities that can be correlated to biological activities. Then, we introduce exciting application examples of membrane-targeting antivirals that have been refined over time and will continue to improve based on biophysical insights. Two ways to abrogate the function of viral membranes are introduced here: (1) selective disruption of the viral membrane structure and (2) alteration of the membrane component. While both methods are suitable for broadly useful antivirals, the latter also has the potential to produce an inactivated vaccine. Collectively, we emphasize how biosensing tools based on membrane interfacial science can provide valuable information that could be translated into biomedicines and improve their selectivity and performance.


Assuntos
Antivirais , Internalização do Vírus , Antivirais/farmacologia , Membranas/química , Desenvolvimento de Vacinas , Lipídeos/análise
12.
Methods Mol Biol ; 2557: 507-518, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36512233

RESUMO

Rab GTPases are key regulators of membrane trafficking. When GTP-bound, or "active," Rabs are anchored to membranes and recruit effector proteins that mediate vesicle formation, transport, and fusion. Rabs are inactivated by GTPase-activating proteins (Rab-GAPs), which catalyze GTP hydrolysis, rendering Rabs cytosolic. In vivo, C-terminal prenylation modifications link activated Rabs to organelle and vesicle membranes, yet historically, in vitro Rab-GAP activity assays have been performed in the absence of membranes. We have developed a method for assaying Rab-GAP activity in a physiological context, with dissociation of the Rab from the membrane serving as a readout for Rab-GAP activity. Given that membrane-binding status is a key consequence of Rab activation state, this assay will be useful for the study of a wide range of Rab/Rab-GAP pairs.


Assuntos
Proteínas Ativadoras de GTPase , Proteínas rab de Ligação ao GTP , Proteínas rab de Ligação ao GTP/metabolismo , Transporte Biológico , Membranas/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Guanosina Trifosfato/metabolismo
13.
Food Res Int ; 162(Pt A): 111924, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36461188

RESUMO

Membrane phase separation forms liquid-ordered (Lo) and liquid-disordered (Ld) phases and is involved in cellular processes and functions. Our previous study has confirmed that peptides can regulate phase separation by increasing the Lo phase. However, the specific mechanisms underlying the phase separation regulation of peptides remain poorly understood. This study aimed to explore the effect of soybean meal peptides on phase separation and illustrate the correlation between phase regulation and membrane localization of the peptides. Phase separation was studied by giant unilamellar vesicles (GUVs), and membrane localization of the peptides was detected by steady-state fluorescence quenching. Our results revealed that peptides YYK, CLA, and SLW enhanced the Lo phase while WLQ decreased the Lo phase. The localization in the membrane amphiphilic region of the peptides played a crucial role in their regulation of phase separation. The more localization of the peptides (YYK, CLA, and SLW) in the membrane amphiphilic region, the stronger the capacity to increase the Lo phase.


Assuntos
Fabaceae , Soja , Lipossomas Unilamelares , Membranas , Peptídeos
14.
JASA Express Lett ; 2(11): 111201, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36456367

RESUMO

The vocal membrane, i.e., an extended part of the vocal fold, is observed in a wide range of species including bats and primates. A theoretical study [Mergell, Fitch, and Herzel (1999). J. Acoust. Soc. Am. 105(3), 2020-2028] predicted that the vocal membranes can make the animal vocalizations more efficient by lowering the phonation threshold pressure. To examine this prediction, a synthetic model of the vocal membrane was developed, and its oscillation properties were examined. The experiments revealed that the phonation threshold pressure was lower in the vocal membrane model compared to that in a model with no vocal membrane. Chaotic oscillations were observed as well.


Assuntos
Quirópteros , Fonação , Animais , Prega Vocal , Membranas , Equipamentos Médicos Duráveis , Exame Físico
15.
Sci Rep ; 12(1): 20749, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456624

RESUMO

We applied a new idea that the potential effect can change the ion adsorption structure on the cell surface to explore the mechanism of digoxin poisoning and the regulation of ion channels. The effects of digoxin on the electrophoretic mobility and behaviors (non-contraction or contraction or autorhythmicity) of cardiomyocytes were observed by single-cell electrophoresis technique (imitate the opening method of in vivo channel) and the method of decomposing surface potential components on the cells. As well as affect the association with electrical activity. The results suggested that the increase of cardiomyocytes transmembrane potential and the Na+-K+ exchange on the cell surface of the action potential phase 4 caused by the poisoning dose of digoxin, leading to the oscillation of adsorbed ions on the cell surface and the incomplete channel structure, which were the mechanism of cardiac ectopic beats. The results revealed that the opening of ion channels is regulated by the surface electric double layer of the cell membrane.


Assuntos
Digoxina , Miócitos Cardíacos , Canais Iônicos , Membranas , Membrana Celular
16.
J Chem Phys ; 157(22): 225102, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36546791

RESUMO

It has been widely accepted that cancer cells are softer than their normal counterparts. This motivates us to propose, as a proof-of-concept, a method for the efficient delivery of therapeutic agents into cancer cells, while normal cells are less affected. The basic idea of this method is to use a water jet generated by the collapse of the bubble under shockwaves to perforate pores in the cell membrane. Given a combination of shockwave and bubble parameters, the cancer membrane is more susceptible to bending, stretching, and perforating than the normal membrane because the bending modulus of the cancer cell membrane is smaller than that of the normal cell membrane. Therefore, the therapeutic agent delivery into cancer cells is easier than in normal cells. Adopting two well-studied models of the normal and cancer membranes, we perform shockwave induced bubble collapse molecular dynamics simulations to investigate the difference in the response of two membranes over a range of shockwave impulse 15-30 mPa s and bubble diameter 4-10 nm. The simulation shows that the presence of bubbles is essential for generating a water jet, which is required for perforation; otherwise, pores are not formed. Given a set of shockwave impulse and bubble parameters, the pore area in the cancer membrane is always larger than that in the normal membrane. However, a too strong shockwave and/or too large bubble results in too fast disruption of membranes, and pore areas are similar between two membrane types. The pore closure time in the cancer membrane is slower than that in the normal membrane. The implications of our results for applications in real cells are discussed in some details. Our simulation may be useful for encouraging future experimental work on novel approaches for cancer treatment.


Assuntos
Simulação de Dinâmica Molecular , Neoplasias , Membrana Celular , Membranas , Água
17.
An. R. Acad. Nac. Farm. (Internet) ; 88(número extraordinario): 53-96, diciembre 2022. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-JHG-313

RESUMO

Los detergentes son anfifilos solubles que poseen la capacidad de solubilizar grasas, dando lugar a micelas mixtas lípido-detergente, que son solubles en agua. Los detergentes son ampliamente utilizados en las industrias alimentaria y de bebidas, textil, médica y farmacéutica, entre otras. En biología molecular, los detergentes son herramientas insustituibles en la solubilización de las membranas celulares y la posterior purificación de proteínas de membrana. La presente revisión resume cuatro décadas de investigación sobre detergentes en el laboratorio de los autores. Una introducción sobre los detergentes y las membranas va seguida por una descripción cuantitativa detallada del mecanismo de solubilización de la membrana por los detergentes, y por una discusión crítica del concepto de membranas resistentes a los detergentes en relación con la hipótesis de las balsas lipídicas (rafts). A continuación, se incluye una sección experimental que resume los principales resultados del grupo de los autores. Finalmente, se describen algunas aplicaciones biofarmacéuticas. Como ejemplo práctico, se discute el uso de jabón de tocador en la prevención de la COVID-19. (AU)


Detergents are soluble amphiphiles that possess the capacity to solubilize fats, giving rise to water-soluble, lipid-detergent mixed micelles. Detergents find an extensive use in food and drink, textile, medical and pharmaceutical industries, among others. In molecular biology, detergents are irreplaceable tools in the solubilization of cell membranes and subsequent membrane protein purification. The present review summarizes four decades of investigation on detergents in the authors’ laboratory. An introduction on detergents and membranes is followed by a detailed, quantitative description of the mechanism of membrane solubilization by detergents, and a critical discussion of the concept of detergent-resistant membranes as related to the lipid raft hypothesis. An experimental section follows, summarizing the main results in the authors’ group. Finally, some biopharmaceutical applications are described. As a working example, the use of toilet soap in the prevention of COVID-19 is discussed. (AU)


Assuntos
Humanos , Detergentes , Tensoativos , Sabões , Membranas , Fosfolipídeos , Micelas
18.
Sci Rep ; 12(1): 21428, 2022 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-36504202

RESUMO

Marseilleviridae is a family of giant viruses, showing a characteristic internal membrane with extrusions underneath the icosahedral vertices. However, such large objects, with a maximum diameter of 250 nm are technically difficult to examine at sub-nanometre resolution by cryo-electron microscopy. Here, we tested the utility of 1 MV high-voltage cryo-EM (cryo-HVEM) for single particle structural analysis (SPA) of giant viruses using tokyovirus, a species of Marseilleviridae, and revealed the capsid structure at 7.7 Å resolution. The capsid enclosing the viral DNA consisted primarily of four layers: (1) major capsid proteins (MCPs) and penton proteins, (2) minor capsid proteins (mCPs), (3) scaffold protein components (ScPCs), and (4) internal membrane. The mCPs showed a novel capsid lattice consisting of eight protein components. ScPCs connecting the icosahedral vertices supported the formation of the membrane extrusions, and possibly act like tape measure proteins reported in other giant viruses. The density on top of the MCP trimer was suggested to include glycoproteins. This is the first attempt at cryo-HVEM SPA. We found the primary limitations to be the lack of automated data acquisition and software support for collection and processing and thus achievable resolution. However, the results pave the way for using cryo-HVEM for structural analysis of larger biological specimens.


Assuntos
Vírus Gigantes , Proteínas do Capsídeo , Microscopia Crioeletrônica , Capsídeo , Membranas
19.
Elife ; 112022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36515266

RESUMO

Piezo1 is the stretch activated Ca2+ channel in red blood cells that mediates homeostatic volume control. Here, we study the organization of Piezo1 in red blood cells using a combination of super-resolution microscopy techniques and electron microscopy. Piezo1 adopts a non-uniform distribution on the red blood cell surface, with a bias toward the biconcave 'dimple'. Trajectories of diffusing Piezo1 molecules, which exhibit confined Brownian diffusion on short timescales and hopping on long timescales, also reflect a bias toward the dimple. This bias can be explained by 'curvature coupling' between the intrinsic curvature of the Piezo dome and the curvature of the red blood cell membrane. Piezo1 does not form clusters with itself, nor does it colocalize with F-actin, Spectrin, or the Gardos channel. Thus, Piezo1 exhibits the properties of a force-through-membrane sensor of curvature and lateral tension in the red blood cell.


Assuntos
Eritrócitos , Canais Iônicos , Canais Iônicos/metabolismo , Fenômenos Mecânicos , Membrana Eritrocítica/metabolismo , Membranas/metabolismo , Mecanotransdução Celular
20.
Langmuir ; 38(50): 15804-15816, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36480923

RESUMO

The local normal to the fluid liquid crystalline phase of the lipid membrane is an axis of motional symmetry for the molecules that make up the bilayer. The presence of cholesterol in the membrane increases not only the lipid hydrocarbon chain order but also the strength of the membrane's orienting potential. Cholesterol undergoes rapid reorientation about a diffusion axis that is roughly aligned with the long molecular axis, but there is also a slower reorientation of the diffusion axis, or "wobble", relative to the local bilayer normal. The extent of this second, slower motion depends on the degree of order of the lipids that make up the bilayer. We use 2H nuclear magnetic resonance of deuterium-labeled cholesterol to investigate quantitatively the effect of lipid chain unsaturation on cholesterol orientation in a series of phospholipid bilayers. We find that the hydrocarbon chains in membranes composed of polyunsaturated lipids are much more highly disordered than those in membranes composed of saturated lipids but that cholesterol remains aligned roughly along the bilayer normal.


Assuntos
Bicamadas Lipídicas , Fosfolipídeos , Bicamadas Lipídicas/química , Fosfolipídeos/química , Espectroscopia de Ressonância Magnética , Membranas , Colesterol/química , Fosfatidilcolinas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...