Mycobacterium species, including Mycobacterium tuberculosis, employs atypical long (C 60-90 ) and branched lipids to produce a complex cell wall and localizes these toward distinct spatial locations, inner membrane (IM) and outer membrane (OM), thus forming a robust permeability barrier. The properties and functional roles of these spatially orchestrated membrane platforms remain unknown. Herein, we report the distinctive lateral organization, fluidity, and lipid domain architecture of protein-free membranes reconstituted from IM and OM lipids in vitro from M. smegmatis (Msm) underscored by their lipid packing and lipid dynamics. We show that Msm OM, against common notion, is more dynamic and fluid compared with IM and reveal the role of cell wall-associated peptidoglycans and lipoarabinomannan on the Msm OM organization. Overall, these studies indicate that mycobacterial species may regulate their overall membrane functionality by regulating the synthesis of these complex arrays of lipids. Based on the structure-function relationship drawn here, documented alteration in the mycobacterial lipidome during cellular infection and/or drug treatment could reflect a mechanism to fine-tune M. tuberculosis membrane properties to its advantage. These findings are expected to inspire development of lipid-centric therapeutic approaches targeted toward its membrane.
Lipids are essential components of cell membranes and govern various membrane functions. Lipid organization within membrane plane dictates recruitment of specific proteins and lipids into distinct nanoclusters that initiate cellular signaling while modulating protein and lipid functions. In addition, one of the most versatile function of lipids is the formation of diverse lipid membrane vesicles for regulating various cellular processes including intracellular trafficking of molecular cargo. In this review, we focus on the various kinds of membrane vesicles in eukaryotes and bacteria, their biogenesis, and their multifaceted functional roles in cellular communication, host-pathogen interactions and biotechnological applications. We elaborate on how their distinct lipid composition of membrane vesicles compared to parent cells enables early and non-invasive diagnosis of cancer andtuberculosis, while inspiring vaccine development and drug delivery platforms. Finally, we discuss the use of membrane vesicles as excellent tools for investigating membrane lateral organization and protein sorting, which is otherwise challenging but extremely crucial for normal cellular functioning. We present current limitations in this field and how the same could be addressed to propel a fundamental and technology-oriented future for extracellular membrane vesicles.
Lipid cell membrane composed of various distinct lipids and proteins act as a platform to assemble various signaling complexes regulating innumerous cellular processes which are strongly downregulated or altered in cancer cells emphasizing the still-underestimated critical function of lipid biomolecules in cancer initiation and progression. In this review, we outline the current understanding of how membrane lipids act as signaling hot spots by generating distinct membrane microdomains called rafts to initiate various cellular processes and their modulation in cancer phenotypes. We elucidate tangible drug targets and pathways all amenable to small-molecule perturbation. Ranging from targeting membrane rafts organization/reorganization to rewiring lipid metabolism and lipid sorting in cancer, the work summarized here represents critical intervention points being attempted for lipid-based anticancer therapy and future directions.
Porous materials that synergistically combine high reversible mechanical elasticity with tunable in situ reaction kinetics can find several biological and industrial applications. However, such materials remain elusive in the literature. Herein, we show that by utilizing the intrinsic elastic property of a 3D macroporous material/scaffold comprising polymer-coated biomimetic ceria nanoparticles, the rate of in situ dephosphorylation reactions can be enhanced efficiently. The elasticity of the scaffold is dynamically controlled by employing compression−decompression, [C−D], cycles.Varying the [C−D] frequency from 0 to 4 increases the formation of dephosphorylation reaction products, such as molecular p-nitrophenol or the in situ self-assembled Fmoc-L-tyrosine-based network. Further, we employ a numerical method improvised on an existing stochastic reaction diffusion approach to explain the unusual increase in product formation as a function of the frequency of the [C−D] cycles. The proposed computational methodology predicts rational design of the enzyme-mimicking material by analyzing the efficiency of the product formation under various absolute amounts of the catalyst and substrate levels, suggesting possible applications of such materials. Finally, as a proof of concept, we demonstrate the use of these materials for culturing mammalian cells, which suggests their potential biological applications after implementing appropriate postsynthetic chemical modifications.
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