Current topics in membranes最新文献

Viruses are subcellular structures that depend on the host cell to replicate, sharing several characteristics with extracellular vesicles (EVs). EVs act in intercellular communication and the regulation of the immune system and can be exploited by viruses as vehicles for transport and dissemination between cells and organs. Although they may favor viral infection, EVs also stand out as potential biomarkers for the diagnosis of viral diseases, as they reflect the physiological and pathological state of the originating cells. These particles can contain viral RNA and specific proteins, allowing for the distinction between different types of infection. Moreover, EVs have great therapeutic potential and are being studied as nanotherapeutic tools due to their low immunogenicity, ability to cross cellular barriers, and ease of modification to allow delivery around the body and tissues. This chapter addresses the interactions between EVs and viruses, as well as the advancements in the use of these structures in diagnosis and the development of new therapeutic strategies. Understanding these mechanisms can significantly contribute to the control of viral infections and the creation of innovative therapies to treat emerging diseases.

Outer membrane vesicles, released by Gram-negative bacteria, have attracted increasing attention in biotechnology due to their structural similarity to bacterial cells, their composition rich in immunogenic factors, and their role in pathogen-host interactions. Although they are involved in multiple functions related to bacterial pathophysiology, their applicability as vaccine platforms has emerged as a promising strategy for the development of next-generation vaccines. OMVs offer significant advantages over traditional vaccines, including the induction of robust T cell-mediated immune responses, the natural presence of pathogen-associated molecular patterns with adjuvant effects, and the possibility of bioengineering to display heterologous antigens. Preclinical trials using OMVs have demonstrated effective protection against infection, highlighting their versatility and safety. In addition, their stability, lack of replicative capacity, and ease of production make OMVs a highly attractive platform, including for emerging diseases and applications in cancer immunotherapy. This chapter discusses the structural and functional aspects of OMVs, with emphasis on their innovative potential in the vaccine field, while also addressing the technological challenges related to their standardization, purification, and industrial scale-up.

Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. are the trypanosomatid parasites responsible for some of the most significant neglected tropical diseases, such as trypanosomiases and leishmaniases, which impact millions of people globally. Alarmingly, some of these diseases have expanded into previously unaffected regions in recent years. These parasites alternate between invertebrate and vertebrate hosts during their life cycles, adapting to different environments and competing with their hosts for several nutrients. To survive, they have evolved complex strategies to acquire essential nutrients, often subverting host immune defenses and overcoming host-imposed nutritional barriers. This chapter explores the membrane-dependent mechanisms of nutrient sensing and uptake in T. brucei, T. cruzi, and Leishmania spp., with an emphasis on how these parasites adapt to nutrient-limited conditions within their host. Following an overview of the challenges posed by host imposed nutrient restrictions, we examine the parasites' membrane-associated processes and metabolic adaptations that enable their survival. The chapter spans a wide range of micro- and macronutrients-lipids, fatty acids, carbohydrates, amino acids, and metals-discussing the roles of membrane proteins in nutrient scavenging, the metabolic pathways they trigger, and their physiological importance for parasite survival, growth, and infectivity. Special attention is given to the mechanisms by which these parasites evade nutritional immunity, a host defense strategy that limits nutrient availability to pathogens. By shedding light on these nutrient acquisition strategies, this chapter aims to advance our understanding of host-parasite interactions and identify potential targets for therapeutic interventions aimed at the metabolic vulnerabilities of these parasites.

Extracellular vesicles (EVs) are membrane-bound nanostructures secreted by various cell types under physiological and pathological conditions. These vesicles carry a diverse cargo of biologically active molecules, including proteins, lipids, nucleic acids, and metabolites. The molecular and structural heterogeneity of EVs presents challenges in fundamental biology, biomarker development, and therapeutic applications. Fungal EVs have gained attention for their roles in pathogenesis, immune modulation, and potential targets for therapies and vaccines. EVs have numerous roles in intercellular communication, facilitated by the transfer of cargo to recipient cells or the interaction of EV surface proteins with cellular receptors. However, the question of how they traverse the cell wall remains a mystery. Fungal EVs can modulate the cell wall through enzymes, contributing to the transition of EVs by the fungal cell wall. As research progresses and technological barriers are overcome, EVs are emerging as valuable targets and promising tools in precision medicine. With continuous improvements in EV isolation, characterization, and manipulation, the next decade is likely to bring significant breakthroughs that will have a profound impact on both basic science and clinical practice.

Extracellular vesicles (EVs) are nano-sized, membrane-surrounded vesicles released by cells under both physiological and pathological conditions. Due to their small size and heterogeneity, comprehensive characterization of EVs remains technically challenging. Among the various analytical tools developed, flow cytometry stands out as a highly versatile and scalable platform, offering high-throughput analysis, multiparametric phenotyping, and quantitative detection. However, conventional flow cytometers are typically designed for cell-sized particles (0.5-40 µm) and require specific optimizations to reliably detect and analyze EVs, which are significantly smaller and result in weaker signals. These optimizations include instrument settings, sample handling and labelling strategies as well as acquisition protocols. Robust calibration and the use of appropriate controls are essential to ensure data accuracy and reproducibility across platforms. In this chapter, we outline the principles, technical considerations, and advantages of applying flow cytometry and imaging flow cytometry to EV research. We also highlight representative applications in both scientific and clinical contexts and discuss future directions for the field.

Entamoeba histolytica, the etiological agent of amoebiasis, is a parasitic protozoan responsible for severe gastrointestinal complications, including colitis and hepatic abscesses. The parasite primarily colonizes the human large intestine, where the active stages confront a hostile environment. Specialized adaptations in the plasma membrane of E. histolytica are critical for survive in this niche and enable the parasite to persist harmlessly in asymptomatic infection or initiate pathogenic interactions that lead to tissue invasion. Early events in pathogenesis are the breaching of the intestinal mucus layer and the subsequent contact with enteric cell. Thes processes have a link to adhesion, and along with concurrent steps such as host cell killing, immune evasion and immunomodulation, depend on the structural and molecular composition of the parasite´s plasma membrane. Over decades, studies on its diverse plasma membrane´s components have unraveled several mechanisms that guarantee the success of E. histolytica as an intestinal pathogen. This chapter explores how factors associated to plasma membrane contribute to the parasite´s ability to thrive in the intestinal environment, evade host defenses, and thrive disease progression.

Giardia intestinalis is an extracellular parasite that inhabits the human intestinal tract, with trophozoite and cyst stages in its life cycle. In this chapter we review basic aspects of structural organization, integrating information of the role of the plasma membrane in various aspects related to its composition, function, and importance at different stages, from the trophozoite form, involvement in encystation, to interactions with the host. Additionally, the membrane's composition, biochemical activities, receptors, and various functions it performs at different stages will be thoroughly explored. The parasite exhibits a unique and fascinating organelle: the peripheral vesicles (PVs). The membranes of these PVs will be explored, foscusing in how they drive endocytic uptake, mediate exocytic release, and carry out lysosomal degradation, all of which are essential for maintaining cellular homeostasis. Additionally, the membranes of the endoplasmic reticulum and their critical role in protein maturation and compartmentalization, both vital for proper cellular functions, will be addressed. Another key role of membranes to be explored is in the encystation process, with the presence of encystation-specific vesicles (ESVs), which are crucial in the life cycle of G. intestinalis, enabling survival in hostile conditions. The transformation of these vesicles and their contribution to protein maturation, ensuring the infectivity and resistance of the parasite, will offer a comprehensive understanding of the mechanisms underlying this parasite's survival and adaptation. The modulation of Giardia's membranes during the adhesion process to host cells will also be addressed, along with the variant surface proteins (VSPs), which are key players in the parasite's immune evasion mechanisms.

Plants release extracellular vesicles and numerous investigations have reported their characterization, either isolated from the apoplastic fluid of different plant sources, the phloem sap or in vitro plant cultures. The term plant derived nanovesicles is applied to vesicles isolated from fruit juices or from homogenized plant tissues/organs. Plant derived nanovesicles share similar components with canonical plant vesicles, including proteins, lipids, nucleic acids, carbohydrates and secondary metabolites, which reflect the composition of the parental tissues/cells. In recent years, several studies have dealt with potential biomedical applications of plant derived nanovesicles, including their use as delivery agents, including vaccines, and their use as therapeutics (like in inflammation conditions and cancer), as well as mediators in regenerative medicine. Furthermore, their use in cosmetics is also gaining attention. Although plant derived nanovesicles have emerged as promising biomaterials for the pharmaceutical industry, critical aspects hinder the rapid translation of basic and preclinical studies to a clinical setting. They include the precise identification of bioactive compounds responsible for the effects detected in vitro, and studies are required to evaluate their effect in humans. In addition, it is necessary to develop protocols to optimize their production in a scalable, sustained and adequate cost-effective relation.