RESUMO
Este trabalho, partindo do tema elaborado, levantou o seguinte problema: As propriedades e vantagens estudadas nas membranas de Hidrogel, se faz desse material eficaz no tratamento dos tecidos periodontais na doença periodontal. Sendo assim, o objetivo deste trabalho foi realizar um levantamento bibliográfico sobre as propriedades e vantagens do uso de membranas de Hidrogel na Regeneração Óssea Guiada nos casos da perda óssea e a recessão gengival associada à Doença Periodontal. O uso de membrana para Regeneração Óssea Guiada (ROG) é um componente essencial do tratamento de doenças periodontais e na regeneração óssea. Neste caso, discutiremos as propriedades dos hidrogéis e seus benefícios e limitações nessa área. Apesar dos desafios significativos existentes, a regeneração óssea baseada em hidrogel é uma grande promessa para o futuro tratamento de doenças e defeitos relacionados aos ossos. Com uma compreensão aprofundada os hidrogéis serão, sem dúvida, uma ferramenta poderosa para o tratamento clínico de defeitos ósseos no futuro.
This study, based on the topic elaborated, raised the following problem: The properties and advantages studied in Hydrogel membranes and if this material can be effective in the treatment of periodontal tissues in periodontal disease. The objective of this work was to perform a bibliographic survey on the properties and advantages of using Hydrogel membranes in Guided Bone Regeneration in cases of bone loss and gingival recession associated with Periodontal Disease. The use of Guided Bone Regeneration (GBR) membrane is an essential component of the treatment of periodontal diseases and bone regeneration. In this case, we discussed the properties of hydrogels and their benefits and limitations in this area. Despite significant challenges, the hydrogel-based bone regeneration holds great promise for the future treatment of bone-related diseases and defects. With in-depth understanding, hydrogels will undoubtedly be a powerful tool for clinical treatment of bone defects in the future.
Assuntos
Doenças Periodontais , Regeneração Óssea , Hidrogéis , MembranasRESUMO
Professor Carlos Gutiérrez-Merino, a prominent scientist working in the complex realm of biological membranes, has made significant theoretical and experimental contributions to the field. Contemporaneous with the development of the fluid-mosaic model of Singer and Nicolson, the Förster resonance energy transfer (FRET) approach has become an invaluable tool for studying molecular interactions in membranes, providing structural insights on a scale of 1-10 nm and remaining important alongside evolving perspectives on membrane structures. In the last few decades, Gutiérrez-Merino's work has covered multiple facets in the field of FRET, with his contributions producing significant advances in quantitative membrane biology. His more recent experimental work expanded the ground concepts of FRET to high-resolution cell imaging. Commencing in the late 1980s, a series of collaborations between Gutiérrez-Merino and the authors involved research visits and joint investigations focused on the nicotinic acetylcholine receptor and its relation to membrane lipids, fostering a lasting friendship.
Assuntos
Lipídeos de Membrana , Receptores Nicotínicos , Membrana Celular/metabolismo , Lipídeos de Membrana/química , Transferência Ressonante de Energia de Fluorescência , Membranas/metabolismo , Receptores Nicotínicos/metabolismoRESUMO
Membrane fusion is a crucial mechanism in a wide variety of important events in cell biology from viral infection to exocytosis. However, despite many efforts and much progress, cell-cell fusion has remained elusive to our understanding. Along the life of the fusion pore, large conformational changes take place from the initial lipid bilayer bending, passing through the hemifusion intermediates, and ending with the formation of the first nascent fusion pore. In this sense, computer simulations are an ideal technique for describing such complex lipid remodeling at the molecular level. In this work, we studied the role played by the muscle-specific membrane protein Myomerger during the formation of the fusion pore. We have conducted µs length atomistic and coarse-grained molecular dynamics, together with free-energy calculations using ad hoc collective variables. Our results show that Myomerger favors the hemifusion diaphragm-stalk transition, reduces the nucleation-expansion energy difference, and promotes the formation of nonenlarging fusion pores.
Assuntos
Bicamadas Lipídicas , Fusão de Membrana , Bicamadas Lipídicas/metabolismo , Fusão de Membrana/fisiologia , Membranas/metabolismo , Simulação de Dinâmica Molecular , Proteínas de Membrana/metabolismo , Proteínas Musculares/metabolismoRESUMO
ABSTRACT Objective: To analyze the morphological and functional long-term outcomes of amniotic membrane transplantation after ocular surface chemical burns. Methods: This prospective study analyzed 7 patients who suffered from severe ocular surface burn and underwent amniotic membrane transplantation from 2015 to 2020 in Hospital de Clínicas - Universidade Federal do Paraná. Results: Out of the seven patients, six (85.7%) suffered unilateral burn and one (14.3%) suffered bilateral burn. Five of them had alkali burns (71.4%), one had acid burn (14.3%) and one suffered gunpowder fireworks burn (14.3%). Mean age was 29.4 years (±standard deviation 13.3, range 14.0 to 47.0 years). Mean visual acuity at first presentation was 1.83±0.79 logMAR (0.015 decimal) and mean VA after a follow-up of 1 year was 0.85±0.70 logMAR (0.141 decimal). The visual acuity significantly improved from 1.83±0.79 to 0.85±0.70 logMAR (p<0.05). Conclusion: Amniotic membrane transplantation is an effective adjunctive treatment in the management of ocular surface chemical burns with potential to improve the final vision outcome.
RESUMO Objetivo: Analisar os resultados morfológicos e funcionais a longo prazo do transplante de membrana amniótica após queimaduras químicas da superfície ocular. Métodos: Foi realizado um estudo prospectivo com análise de sete pacientes que sofreram queimaduras graves da superfície ocular e foram submetidos a transplante de membrana amniótica no período de 2015 a 2020 no Hospital de Clínicas da Universidade Federal do Paraná. Resultados: Dos sete pacientes, seis (85,7%) sofreram queimadura unilateral e um (14,3%) sofreu queimadura bilateral. Cinco deles sofreram queimaduras por álcali (71,4%), um por ácido (14,3%) e um por pólvora de fogo de artifício (14,3%). A média de idade foi de 29,4 anos (±desvio-padrão de 13,3, intervalo de 14,0 a 47,0 anos). A acuidade visual média na primeira apresentação foi de 1,83±0,79 logMAR (0,015 decimal) e, após 1 ano de seguimento, foi de 0,85±0,70 logMAR (0,141 decimal). A acuidade visual melhorou significativamente, de 1,83±0,79 para 0,85±0,70 logMAR (p<0,05). Conclusão: O transplante de membrana amniótica é um tratamento adjuvante eficaz no manejo de queimaduras químicas da superfície ocular com potencial para melhorar a visão final.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Oftalmológicos/métodos , Queimaduras Químicas/cirurgia , Queimaduras Oculares/cirurgia , Queimaduras Oculares/induzido quimicamente , Córnea/cirurgia , Âmnio/transplante , Preservação de Tecido , Acuidade Visual , Estudos Prospectivos , Membranas/transplanteRESUMO
A meningite é um processo inflamatório que acomete as meninges, membranas que recobrem o cérebro e a medula espinhal. Um total de 1,3 milhão de casos de meningite ocorrem por ano em todo o mundo. Este estudo teve como objetivo analisar o perfil epidemiológico dos casos de meningite na população pediátrica na cidade de São Paulo, realizar uma análise dos dados e identificar possível associação entre a densidade demográfica da cidade de São Paulo e os casos de meningite na região. Foram incluídos nesse estudo dados do período de 2017 a 2023, extraídos do banco de dados do departamento de informática do Sistema Único de Saúde do Brasil (DataSUS). Todos os testes foram executados com o auxílio do software Bioestat 5.5. Os resultados com p ≤ 0,05 (bilateral) foram considerados estatisticamente significativos. A análise revelou uma tendência a diminuição do número de casos de meningite na população pediátrica entre os anos de 2017 a 2023 na cidade de São Paulo quando comparado com a densidade populacional no período avaliado. O perfil epidemiológico desses pacientes mostrou maior acometimento no sexo masculino, na raça branca e com maior incidência em menores de 1 ano de idade. Em relação a etiologia, houve predomínio da etiologia viral, sendo que a maioria dos casos evoluíram com alta. Logo, os achados dessa pesquisa reforçam a importância de estratégias de saúde pública para a população pediátrica, uma vez que os dados mostraram uma redução do número de casos com as medidas até então implantadas. Apesar da diminuição de casos de meningite na população pediátrica, recomenda-se maior investimento em programas de prevenção, diagnóstico e tratamento direcionados a população vulnerável descrita no presente estudo, uma vez que ainda se nota uma taxa de letalidade importante, principalmente na população menor de 1 ano de idade. Palavras-chave: Perfil Epidemiológico. Meningite na população pediátrica. Meningite-Epidemiologia. Sistema Único de Saúde (SUS). São Paulo (Cidade).
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Pediatria , Medula Espinal , Terapêutica , Sistema Único de Saúde , Perfil de Saúde , Incidência , Mortalidade , Densidade Demográfica , Estratégias de Saúde , Menores de Idade , Populações Vulneráveis , Grupos Raciais , Prevenção de Doenças , Cérebro , Análise de Dados , Investimentos em Saúde , Membranas , Meningite , MeningesRESUMO
Boosted by the indiscriminate use of antibiotics, multidrug-resistance (MDR) demands new strategies to combat bacterial infections, such as photothermal therapy (PTT) based on plasmonic nanostructures. PTT efficiency relies on photoinduced damage caused to the bacterial machinery, for which nanostructure incorporation into the cell envelope is key. Herein, we shall unveil the binding and photochemical mechanisms of gold shell-isolated nanorods (AuSHINRs) on bioinspired bacterial membranes assembled as Langmuir and Langmuir-Schaefer (LS) monolayers of DOPE, Lysyl-PG, DOPG and CL. AuSHINRs incorporation expanded the isotherms, with stronger effect on the anionic DOPG and CL. Indeed, FTIR of LS films revealed more modifications for DOPG and CL owing to stronger attractive electrostatic interactions between anionic phosphates and the positively charged AuSHINRs, while electrostatic repulsions with the cationic ethanolamine (DOPE) and lysyl (Lysyl-PG) polar groups might have weakened their interactions with AuSHINRs. No statistical difference was observed in the surface area of irradiated DOPE and Lysyl-PG monolayers on AuSHINRs, which is evidence of the restricted nanostructures insertion. In contrast, irradiated DOPG monolayer on AuSHINRs decreased 4.0 % in surface area, while irradiated CL monolayer increased 3.7 %. Such results agree with oxidative reactions prompted by ROS generated by AuSHINRs photoactivation. The deepest AuSHINRs insertion into DOPG may have favored chain cleavage while hydroperoxidation is the mostly like outcome in CL, where AuSHINRs are surrounding the polar groups. Furthermore, preliminary experiments on Escherichia coli culture demonstrated that the electrostatic interactions with AuSHINRs do not inhibit bacterial growth, but the photoinduced effects are highly toxic, resulting in microbial inactivation.
Assuntos
Nanoestruturas , Nanotubos , Ouro , Membranas , Membrana Celular , Escherichia coliRESUMO
AIM: To assess the correlation between the periodontal phenotype (PP) and sinus membrane thickness (SMT) in humans. METHODS: This review was conducted according to the PRISMA guidelines. Two reviewers independently carried out electronic and manual literature searches of studies published in English, German, and Spanish, from 1970 to September 2022 in four electronic databases, PubMed/Medline, Scopus, Cochrane Library, and Web of Science, in addition to gray literature. Studies that assessed the correlation between PP and SMT in adults (aged 18 years) were included. Methodological quality was evaluated using the Appraisal Tool for Cross-Sectional Studies (AXIS) for articles that met the eligibility criteria. RESULTS: Six studies, including 510 patients, were considered for qualitative analysis. All included studies were cross-sectional, and the correlation between the PP and SMT was evaluated, finding a positive and high correlation in 83.3% of them, based on a value of ≥0.7. All the included studies were assessed with a high overall risk of bias. CONCLUSIONS: Periodontal phenotype and sinus membrane thickness are likely correlated. Nevertheless, further standardized studies are required to draw definitive conclusions.
Assuntos
Membranas , Adulto , Humanos , FenótipoRESUMO
The brain is commonly understood as a complex network system with a particular organization and topology that can result in specific electrophysiological patterns. Among all the dynamic elements resulting from the circuits of the brain's network, ephapticity is a cellular communication mechanism that has received little attention. To understand the network's properties of ephaptic entrainment, we start investigating the ephaptic effect on a single neuron. In this study, we used numerical simulations to examine the relationship between alterations in ephaptic neuronal entrainment and impaired electrophysiological properties of the neuronal membrane, which can occur via spike field coherence (SFC). This change in frequency band amplitude is observed in some neurodegenerative diseases, such as Parkinson's or Alzheimer's. To further investigate these phenomena, we proposed a damaged model based on the impairment of both the resistance of the ion channels and the capacitance of the lipid membrane. Therefore, we simulated ephaptic entrainment with the hybrid neural model quadratic integrate-and-fire ephaptic (QIF-E), which mimics an ephaptic entrainment generated by an LFP (simulate a neuronal group). Our results indicate a link between peak entrainment (ephapticity) preference and a shift in frequency band when damage occurs mainly in ion channels. Finally, we discuss possible relationships between ephaptic entrainment and neurodegenerative diseases associated with aging factors.
Assuntos
Neurônios , Fatores Etários , Encéfalo , MembranasRESUMO
Using a flexibility prediction algorithm and in silico structural modeling, we have calculated the intrinsic flexibility of several magainin derivatives. In the case of magainin-2 (Mag-2) and magainin H2 (MAG-H2) we have found that MAG-2 is more flexible than its hydrophobic analog, Mag-H2. This affects the degree of bending of both peptides, with a kink around two central residues (R10, R11), whereas, in Mag-H2, W10 stiffens the peptide. Moreover, this increases the hydrophobic moment of Mag-H2, which could explain its propensity to form pores in POPC model membranes, which exhibit near-to-zero spontaneous curvatures. Likewise, the protective effect described in DOPC membranes for this peptide regarding its facilitation in pore formation would be related to the propensity of this lipid to form membranes with negative spontaneous curvature. The flexibility of another magainin analog (MSI-78) is even greater than that of Mag-2. This facilitates the peptide to present a kind of hinge around the central F12 as well as a C-terminal end prone to be disordered. Such characteristics are key to understanding the broad-spectrum antimicrobial actions exhibited by this peptide. These data reinforce the hypothesis on the determinant role of spontaneous membrane curvature, intrinsic peptide flexibility, and specific hydrophobic moment in assessing the bioactivity of membrane-active antimicrobial peptides.
Assuntos
Bicamadas Lipídicas , Proteínas de Xenopus , Magaininas/química , Proteínas de Xenopus/análise , Proteínas de Xenopus/química , Membranas/química , Bicamadas Lipídicas/químicaRESUMO
Cell membranes are quasi-bidimensional soft systems formed by multipoles in an ordered array that can be polarized in an electric field. Consequently, electrostatic potentials emerge inside membranes, and membranes respond to external electric fields. From a mechanical perspective, membranes can be easily compressed-expanded, laterally deformed, and curved. Bending is particularly easy, and this kind of deformation translates to changes in the relative positions of the negative and positive charges, leading to strain gradient-induced polarization. Conversely, an external electric field gradient will exert a bending stress that translates to mechanical membrane deformation. These phenomena are described through membrane flexoelectricity. Here, we describe this property in lipid bilayers and cell membranes and summarize the studies in the field with emphasis on the effects promoted by membrane asymmetry.
Assuntos
Eletricidade , Bicamadas Lipídicas , Eletricidade Estática , Bicamadas Lipídicas/metabolismo , Membrana Celular/metabolismo , Membranas/metabolismoRESUMO
Cationic and amphiphilic peptides can be used as homing devices to accumulate conjugated antibiotics to bacteria-enriched sites and promote efficient microbial killing. However, just as important as tackling bacterial infections, is the modulation of the immune response in this complex microenvironment. In the present report, we designed a peptide chimaera called Chim2, formed by a membrane-active module, an enzyme hydrolysis site and a formyl peptide receptor 2 (FPR2) agonist. This molecule was designed to adsorb onto bacterial membranes, promote their lysis, and upon hydrolysis by local enzymes, release the FPR2 agonist sequence for activation and recruitment of immune cells. We synthesized the isolated peptide modules of Chim2 and characterized their biological activities independently and as a single polypeptide chain. We conducted antimicrobial assays, along with other tests aiming at the analyses of the cellular and immunological responses. In addition, assays using vesicles as models of eukaryotic and prokaryotic membranes were conducted and solution structures of Chim2 were generated by 1H NMR. Chim2 is antimicrobial, adsorbs preferentially to negatively charged vesicles while adopting an α-helix structure and exposes its disorganized tail to the solvent, which facilitates hydrolysis by tryptase-like enzymes, allowing the release of the FPR2 agonist fragment. This fragment was shown to induce accumulation of the cellular activation marker, lipid bodies, in mouse macrophages and the release of immunomodulatory interleukins. In conclusion, these data demonstrate that peptides with antimicrobial and immunomodulatory activities can be considered for further development as drugs.
Assuntos
Anti-Infecciosos , Receptores de Formil Peptídeo , Animais , Camundongos , Antibacterianos/farmacologia , Anti-Infecciosos/química , Bactérias , Membranas , Receptores de Formil Peptídeo/antagonistas & inibidoresRESUMO
The discovery of the endocannabinoid system (ECS) dates back only 30 years. Although many research groups have been elucidating its components, location, functions and metabolism, the peculiarities of the compounds considered "neurotransmitters" of ECS generate questions that have not yet been answered or controversies in the literature. In this context, we studied the molecular behaviour of the main endocannabinoid compounds and the main phytocannabinoids in eukaryotic outer and inner model membranes. The high lipophilicity of these compounds gives place to the hypothesis that cannabinoids may reach the molecular targets through the lipid bilayer. This consideration is not only for the cannabinoid receptors but also for other (many) targets that these bioactive molecules modulate (Watkins, 2019; Nelson et al., 2020; Jakowiecki and Filipek, 2016). Given the reported multitarget action of these compounds and the differential behaviour towards the different receptors, studying the properties and dynamics of these cannabinoids in POPC and POPE model membranes become relevant. In this regard, we have studied the differential modulation of the endocannabinoids anandamide and 2-arachidonoyl-glycerol and the phytocannabinoids cannabidiol and trans-Δ9-tetrahydrocannabinol to eukaryotic outer and inner model membranes. Results show that behaviours favour the mobility of the bioactive molecules studied by the external eukaryotic model membrane. As well as, the internal eukaryotic model membrane is less fluid, favouring the stabilisation of folded conformations or the positioning of the molecules in the centre of the bilayer. These results provide relevant evidence that contributes to a deep inside understanding of the behaviour of the primary endogenous ligands of ECS, together with the principal phytocannabinoids of C. sativa.
Assuntos
Canabidiol , Endometriose , Feminino , Humanos , Endocanabinoides , Membranas , DronabinolRESUMO
We describe a gland in the arthrodial membrane of the coxa-trochanter articulation in the fourth pair of legs in the Neotropical harvester Mischonyx squalidus Bertkau, 1880. Externally the glandular area has a rough appearance with pores on its surface, with folds of the arthrodial membrane. Internally, its secretory cells have spherical secretory vesicles, smooth endoplasmic reticulum, mitochondria and ducts that exit from the cells and cross the arthrodial membrane. Histochemical tests indicate the presence of proteins and neutral glycoproteins. The function of the gland might be to produce lubricating products that allow better movement of the coxa-trochanter region.
Assuntos
Humanos , Aracnídeos/anatomia & histologia , Lubrificação , Membranas/anatomia & histologiaRESUMO
BACKGROUND: The location of the cricothyroid membrane plays a fundamental role in the scenario of a difficult airway in the non-ventilated/ non-intubated situation. With the use of ultrasound, the membrane can be located easily by trained operators. MATERIAL AND METHODS: 82 patients with morbid obesity were studied, as it is a population with a higher incidence of difficult intubation. First, an operator made a marking based on anatomical landmarks. A different ultrasound-trained operator located the cricothyroid membrane with US. The difference in millimeters between both measurements was compared. RESULTS: In the 82 patients, 100% located the cricothyroid membrane by US. When comparing both techniques, a difference of 5.8 ± 3.2 mm (p > 0.05) was found. CONCLUSION: The use of ultrasound for the evaluation of the airway is a non-invasive and useful technique that allows the identification of the cricothyroid membrane.
INTRODUCCIÓN: La ubicación de la membrana cricotiroidea cumple un rol fundamental en el escenario de una vía aérea difícil en la situación no ventilo/no intubo. Con el uso de ultrasonido la membrana puede ubicarse de manera fácil y expedita por operadores entrenados. MATERIAL Y MÉTODOS: Se estudian 82 pacientes portadores de obesidad mórbida, por ser una población con mayor incidencia de intubación difícil. Primero, un operador realizó una marcación basándose en reparos anatómicos. Luego otro operador entrenado en ultrasonido ubicó la membrana cricotiroidea por ultrasonido. Se comparó la diferencia en milímetros entre ambas mediciones. RESULTADOS: En los 82 pacientes al 100% se les ubicó la membrana cricotiroidea. Al comparar ambas técnicas se encontró una diferencia de 5,8 ± 3,2 mm (p > 0,05). CONCLUSIÓN: El uso de ultrasonido para la evaluación de vía aérea es una técnica no invasiva y útil que permite identificar la membrana cricotiroidea.
Assuntos
Humanos , Masculino , Feminino , Adulto , Cartilagem Tireóidea/diagnóstico por imagem , Obesidade Mórbida/complicações , Ultrassonografia/métodos , Cartilagem Cricoide/diagnóstico por imagem , Manuseio das Vias Aéreas/métodos , Palpação , Estudos Prospectivos , Intubação Intratraqueal , Membranas/diagnóstico por imagemRESUMO
The use of selective barriers as resorbable membranes has become a routine clinical procedure for guided bone regeneration. Therefore, the production of membranes with a low inflammatory potential during their resorption process has become the goal of a considerable number of researches. Aim: The purpose of the present study was to evaluate the biocompatibility of poly (L- lactic acid) (PLLA) and biocelulose membranes (BC) inserted in the subcutaneous tissue on the dorsum of rats. Methods: Fifteen animals underwent surgical procedures for the insertion of 4 types of membranes: COL (Collagen membrane) Control Group; BC (Biocellulose membrane); BCAg (Biocellulose membrane impregnated with Silver); PLLA (Poly (L-lactic acid) membrane). All membrane types were inserted into each animal. Animals were euthanized after 3, 7, and 15 days of the surgical procedure. Descriptive histological analyses were carried out to investigate host tissue reaction to membrane presence by assessing the anti-inflammatory process composition associated with the membrane resorption and the presence of foreign-body reaction or encapsulation. Results: The BC membranes showed a higher degree of inflammation and poor pattern of integration with the surrounding tissues than the PLLA and COL membranes. Conclusion: The PLLA and COL membranes present better biocompatibility than the BC membranes
Assuntos
Animais , Ratos , Materiais Biocompatíveis/análise , Regeneração Óssea , Teste de Materiais , Ácido Láctico , Tela Subcutânea , Membranas , Celulose , InflamaçãoRESUMO
Crossing the cellular membrane is one of the main barriers during drug discovery; many potential drugs are rejected for their inability to integrate into the intracell fluid. Although many solutions have been proposed to overcome this barrier, arguably the most promising solution is the use of cell-penetrating peptides. Recently, an array of hydrophobic penetrating peptides was discovered via high throughput screening which proved to be able to cross the membrane passively, and although these peptides proved to be effective at penetrating the cell, the details behind the underlying mechanism of this process remain unknown. In this study, we developed a method to find the equilibrium structure at the transmembrane domain of TP1, a hydrophobic penetrating peptide. In this method, we selectively deuterium-label amino acids in the peptidic chain, and employ results of [Formula: see text]H-NMR spectroscopy to find a molecular dynamics simulation of the peptide that reproduces the experimental results. Effectively finding the equilibrium orientation and dynamics of the peptide in the membrane. We employed this equilibrium structure to simulate the entire translocation mechanism and found that after the peptide reaches its equilibrium structure, it must undergo a two-step mechanism in order to completely translocate the membrane, each step involving the flip-flop of each arginine residue in the peptide. This leads us to conclude that the RLLR motif is essential for the translocating activity of the peptide.
Assuntos
Peptídeos Penetradores de Células , Membrana Celular/metabolismo , Membranas/metabolismo , Peptídeos Penetradores de Células/química , Simulação de Dinâmica Molecular , Interações Hidrofóbicas e HidrofílicasRESUMO
This review is an attempt to incorporate water as a structural and thermodynamic component of biomembranes. With this purpose, the consideration of the membrane interphase as a bidimensional hydrated polar head group solution, coupled to the hydrocarbon region allows for the reconciliation of two theories on cells in dispute today: one considering the membrane as an essential part in terms of compartmentalization, and another in which lipid membranes are not necessary and cells can be treated as a colloidal system. The criterium followed is to describe the membrane state as an open, non-autonomous and responsive system using the approach of Thermodynamic of Irreversible Processes. The concept of an open/non-autonomous membrane system allows for the visualization of the interrelationship between metabolic events and membrane polymorphic changes. Therefore, the Association Induction Hypothesis (AIH) and lipid properties interplay should consider hydration in terms of free energy modulated by water activity and surface (lateral) pressure. Water in restricted regions at the lipid interphase has thermodynamic properties that explain the role of H-bonding networks in the propagation of events between membrane and cytoplasm that appears to be relevant in the context of crowded systems.
Assuntos
Lipídeos , Água , Bicamadas Lipídicas/química , Lipídeos/química , Membranas/química , Termodinâmica , Água/químicaRESUMO
Recent studies revealed that molecular events related with the physiology and pathology of αS might be regulated by specific sequence motifs in the primary sequence of αS. The importance of individual residues in these motifs remains an important open avenue of investigation. In this work, we have addressed the structural details related to the amyloid fibril assembly and lipid-binding features of αS through the design of site-directed mutants at position 39 of the protein and their study by in vitro and in vivo assays. We demonstrated that aromaticity at position 39 of αS primary sequence influences strongly the aggregation properties and the membrane-bound conformations of the protein, molecular features that might have important repercussions for the function and dysfunction of αS. Considering that aggregation and membrane damage is an important driver of cellular toxicity in amyloid diseases, future work is needed to link our findings with studies based on toxicity and neuronal cell death. BRIEF STATEMENT OUTLINING SIGNIFICANCE: Modulation by distinct sequential motifs and specific residues of αS on its physiological and pathological states is an active area of research. Here, we demonstrated that aromaticity at position 39 of αS modulates the membrane-bound conformations of the protein, whereas removal of aromatic functionality at position 39 reduces strongly the amyloid assembly in vitro and in vivo. Our study provides new evidence for the modulation of molecular events related with the physiology and pathology of αS.
Assuntos
Amiloide , alfa-Sinucleína , Amiloide/genética , Amiloide/metabolismo , Membranas/metabolismo , Ligação Proteica , Estrutura Secundária de Proteína , alfa-Sinucleína/químicaRESUMO
Combining single cell experiments, population dynamics and theoretical methods of membrane mechanics, we put forward that the rate of cell proliferation in E. coli colonies can be regulated by modifiers of the mechanical properties of the bacterial membrane. Bacterial proliferation was modelled as mediated by cell division through a membrane constriction divisome based on FtsZ, a mechanically competent protein at elastic interaction against membrane rigidity. Using membrane fluctuation spectroscopy in the single cells, we revealed either membrane stiffening when considering hydrophobic long chain fatty substances, or membrane softening if short-chained hydrophilic molecules are used. Membrane stiffeners caused hindered growth under normal division in the microbial cultures, as expected for membrane rigidification. Membrane softeners, however, altered regular cell division causing persistent microbes that abnormally grow as long filamentous cells proliferating apparently faster. We invoke the concept of effective growth rate under the assumption of a heterogeneous population structure composed by distinguishable individuals with different FtsZ-content leading the possible forms of cell proliferation, from regular division in two normal daughters to continuous growing filamentation and budding. The results settle altogether into a master plot that captures a universal scaling between membrane rigidity and the divisional instability mediated by FtsZ at the onset of membrane constriction.
Assuntos
Membrana Celular/metabolismo , Proliferação de Células/fisiologia , Escherichia coli/crescimento & desenvolvimento , Proteínas de Bactérias/metabolismo , Proteínas de Ciclo Celular/metabolismo , Divisão Celular/genética , Divisão Celular/fisiologia , Membrana Celular/fisiologia , Proteínas do Citoesqueleto/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Membrana/metabolismo , Membranas/metabolismoRESUMO
It is established that coronaviruses are transmitted most through aerosols produced when an infected individual coughs or sneezes.1 Although there is no clear evidence of person-to-person airborne transmission, it is possible that part of this component could be due to microscopic respiratory droplets at short to medium distances (up to several meters, or room scale) and deposits from respiratory droplets on surfaces.2,3 However, recent studies revealed that infected patients can potentially be a source of the virus not only through respiratory but also fecaloral or body fluid routes, raising also the theoretical possibility of bloodborne transmission.4 Based on these arguments, the possibility has also been raised of some equipment that could be a new source of transmission, like the membranes used for extracorporeal oxygenation, which act the same as lungs and also have a direct contact with the blood. Most centers worldwide report a reduction in the cardiac procedures due to the pandemic, however emergency surgeries with conventional cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) procedures have been performed every day. Despite guidelines and modifications for operating theatre preparation for the management of suspected or confirmed SARS-CoV-2 patients submitted to cardiac surgery, many aspects still need to be clarified.5 Potential risk of transmission with these membranes exists, so much that Dres et al.6 reported a study evaluating the risks of SARS-CoV-2 dissemination through membranes used for extra corporeal organ support in critically ill patients, within 48 h after ECMO and continuous renal replacement therapy (CRRT) initiation. They investigated whether SARS-CoV-2 RNA was detected in the dialysis effluent fluid or in the condensate collected from the ECMO membrane gas outlet, when the virus was present in the lower respiratory tract and the plasma. Results showed that in 25 patients on veno-venous ECMO, SARSCoV-2 RNA was not detected in the membrane oxygenator gas outlet condensate in any of 25 patients of whom 13 were plasma RNA positive. Also, they were not able to measure any SARS-CoV-2 RNA in the dialysate of those patients who additionally were treated by CRRT.