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Theranostics 2021Exosomes are cell-derived nanovesicles that are involved in the intercellular transportation of materials. Therapeutics, such as small molecules or nucleic acid drugs,... (Review)
Review
Exosomes are cell-derived nanovesicles that are involved in the intercellular transportation of materials. Therapeutics, such as small molecules or nucleic acid drugs, can be incorporated into exosomes and then delivered to specific types of cells or tissues to realize targeted drug delivery. Targeted delivery increases the local concentration of therapeutics and minimizes side effects. Here, we present a detailed review of exosomes engineering through genetic and chemical methods for targeted drug delivery. Although still in its infancy, exosome-mediated drug delivery boasts low toxicity, low immunogenicity, and high engineerability, and holds promise for cell-free therapies for a wide range of diseases.
Topics: Animals; Drug Delivery Systems; Exosomes; Humans; Membrane Proteins; Membranes; Protein Engineering
PubMed: 33537081
DOI: 10.7150/thno.52570 -
The Journal of Membrane Biology Jun 2018Biomembranes assemble and operate at the interface with electrolyte solutions. Interactions between ions in solutions and the lipid affect the membrane structure,...
Biomembranes assemble and operate at the interface with electrolyte solutions. Interactions between ions in solutions and the lipid affect the membrane structure, dynamics and electrostatic potential. In this article, I review some of the experimental and computational methods that are used to study membrane-ions interactions. Experimental methods that account for membrane-ion interactions directly and indirectly are presented first. Then, studies in which molecular dynamics simulations were used to gain an understanding of membrane-ion interactions are surveyed. Finally, the current view on membrane-ion interactions and their significance is briefly discussed.
Topics: Ions; Magnetic Resonance Spectroscopy; Membranes; Molecular Dynamics Simulation
PubMed: 29330605
DOI: 10.1007/s00232-017-0010-y -
Biochimica Et Biophysica Acta.... Mar 2023Proteins can organize into dynamic, functionally important assemblies on fluid membrane surfaces. Phase separation has emerged as an important mechanism for forming such... (Review)
Review
Proteins can organize into dynamic, functionally important assemblies on fluid membrane surfaces. Phase separation has emerged as an important mechanism for forming such protein assemblies on the membrane during cell signaling, endocytosis, and cytoskeleton regulation. Protein-protein phase separation thus adds novel fluid mosaics to the classical Singer and Nicolson model. Protein condensates formed in this process can modulate membrane morphologies. This is evident from recent reports of protein condensate-driven membrane reshaping in processes such as endocytosis, autophagosome formation, and protein storage vacuole morphogenesis in plants. Lateral phase separation (on the membrane surface) of peripheral curvature coupling proteins can modulate such membrane morphological transitions. Additionally, three-dimensional protein phase separation can result in droplets that through adhesion can affect membrane shape changes. How do these condensate-driven curvature generation mechanisms contrast with the classically recognized scaffolding and amphipathic helix insertion activities of specific membrane remodeling proteins? A salient feature of these condensate-driven membrane activities is that they depend upon both macroscopic features (such as interfacial energies of the condensate, membrane, and cytosol) as well as microscopic, molecular-level interactions (such as protein-lipid binding). This review highlights the current understanding of the mechanisms underlying curvature generation by protein condensates in various biological pathways.
Topics: Membrane Proteins; Membranes
PubMed: 36642341
DOI: 10.1016/j.bbamem.2023.184121 -
Molecules (Basel, Switzerland) Aug 2022This review is an attempt to incorporate water as a structural and thermodynamic component of biomembranes. With this purpose, the consideration of the membrane... (Review)
Review
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.
Topics: Lipid Bilayers; Lipids; Membranes; Thermodynamics; Water
PubMed: 35956945
DOI: 10.3390/molecules27154994 -
Journal of Structural Biology Oct 2016In bacteria the ability to remodel membrane underpins basic cell processes such as growth, and more sophisticated adaptations like inter-cell crosstalk, organelle... (Review)
Review
In bacteria the ability to remodel membrane underpins basic cell processes such as growth, and more sophisticated adaptations like inter-cell crosstalk, organelle specialisation, and pathogenesis. Here, selected examples of membrane remodelling in bacteria are presented and the diverse mechanisms for inducing membrane fission, fusion, and curvature discussed. Compared to eukaryotes, relatively few curvature-inducing proteins have been characterised so far. Whilst it is likely that many such proteins remain to be discovered, it also reflects the importance of alternative membrane remodelling strategies in bacteria where passive mechanisms for generating curvature are utilised.
Topics: Bacteria; Membrane Proteins; Membranes
PubMed: 27265614
DOI: 10.1016/j.jsb.2016.05.010 -
Journal of Structural Biology Mar 2022Protein transport between the membranous compartments of the eukaryotic cells is mediated by the constant fission and fusion of the membrane-bounded vesicles from a... (Review)
Review
Protein transport between the membranous compartments of the eukaryotic cells is mediated by the constant fission and fusion of the membrane-bounded vesicles from a donor to an acceptor membrane. While there are many membrane remodelling complexes in eukaryotes, COPII, COPI, and clathrin-coated vesicles are the three principal classes of coat protein complexes that participate in vesicle trafficking in the endocytic and secretory pathways. These vesicle-coat proteins perform two key functions: deforming lipid bilayers into vesicles and encasing selective cargoes. The three trafficking complexes share some commonalities in their structural features but differ in their coat structures, mechanisms of cargo sorting, vesicle formation, and scission. While the structures of many of the proteins involved in vesicle formation have been determined in isolation by X-ray crystallography, elucidating the proteins' structures together with the membrane is better suited for cryogenic electron microscopy (cryo-EM). In recent years, advances in cryo-EM have led to solving the structures and mechanisms of several vesicle trafficking complexes and associated proteins.
Topics: Coat Protein Complex I; Cryoelectron Microscopy; Crystallography, X-Ray; Membranes; Protein Transport
PubMed: 35101600
DOI: 10.1016/j.jsb.2022.107836 -
International Journal of Molecular... Jul 2022Eukaryotic cells contain membranes with various curvatures, from the near-plane plasma membrane to the highly curved membranes of organelles, vesicles, and membrane... (Review)
Review
Eukaryotic cells contain membranes with various curvatures, from the near-plane plasma membrane to the highly curved membranes of organelles, vesicles, and membrane protrusions. These curvatures are generated and sustained by curvature-inducing proteins, peptides, and lipids, and describing these mechanisms is an important scientific challenge. In addition to that, some molecules can sense membrane curvature and thereby be trafficked to specific locations. The description of curvature sensing is another fundamental challenge. Curved lipid membranes and their interplay with membrane-associated proteins can be investigated with molecular dynamics (MD) simulations. Various methods for simulating curved membranes with MD are discussed here, including tools for setting up simulation of vesicles and methods for sustaining membrane curvature. The latter are divided into methods that exploit scaffolding virtual beads, methods that use curvature-inducing molecules, and methods applying virtual forces. The variety of simulation tools allow researcher to closely match the conditions of experimental studies of membrane curvatures.
Topics: Cell Membrane; Lipid Bilayers; Membranes; Molecular Dynamics Simulation; Proteins
PubMed: 35897670
DOI: 10.3390/ijms23158098 -
Journal of Magnetic Resonance (San... Jul 2017The advancement in site-directed spin labeling of proteins has enabled EPR studies to expand into newer research areas within the umbrella of protein-membrane... (Review)
Review
The advancement in site-directed spin labeling of proteins has enabled EPR studies to expand into newer research areas within the umbrella of protein-membrane interactions. Recently, membrane remodeling by amyloidogenic and non-amyloidogenic proteins has gained a substantial interest in relation to driving and controlling vital cellular processes such as endocytosis, exocytosis, shaping of organelles like endoplasmic reticulum, Golgi and mitochondria, intracellular vesicular trafficking, formation of filopedia and multivesicular bodies, mitochondrial fusion and fission, and synaptic vesicle fusion and recycling in neurotransmission. Misregulation in any of these processes due to an aberrant protein (mutation or misfolding) or alteration of lipid metabolism can be detrimental to the cell and cause disease. Dissection of the structural basis of membrane remodeling by proteins is thus quite necessary for an understanding of the underlying mechanisms, but it remains a formidable task due to the difficulties of various common biophysical tools in monitoring the dynamic process of membrane binding and bending by proteins. This is largely since membranes generally complicate protein structure analysis and this problem is amplified for structural analysis in the presence of different types of membrane curvatures. Recent EPR studies on membrane remodeling by proteins show that a significant structural information can be generated to delineate the role of different protein modules, domains and individual amino acids in the generation of membrane curvature. These studies also show how EPR can complement the data obtained by high resolution techniques such as X-ray and NMR. This perspective covers the application of EPR in recent studies for understanding membrane remodeling by amyloidogenic and non-amyloidogenic proteins that is useful for researchers interested in using or complimenting EPR to gain better understanding of membrane remodeling. We also discuss how a single protein can generate different type of membrane curvatures using specific conformations for specific membrane structures and how EPR is a versatile tool well-suited to analyze subtle alterations in structures under such modifying conditions which otherwise would have been difficult using other biophysical tools.
Topics: Amyloidogenic Proteins; Animals; Electron Spin Resonance Spectroscopy; Humans; Membrane Proteins; Membranes; Models, Molecular; Spin Labels
PubMed: 28579098
DOI: 10.1016/j.jmr.2017.02.014 -
Nature Communications Nov 2022The plasma membrane's main constituents, i.e., phospholipids and membrane proteins, are known to be organized in lipid-protein functional domains and supercomplexes. No...
The plasma membrane's main constituents, i.e., phospholipids and membrane proteins, are known to be organized in lipid-protein functional domains and supercomplexes. No active membrane-intrinsic process is known to establish membrane organization. Thus, the interplay of thermal fluctuations and the biophysical determinants of membrane-mediated protein interactions must be considered to understand membrane protein organization. Here, we used high-speed atomic force microscopy and kinetic and membrane elastic theory to investigate the behavior of a model membrane protein in oligomerization and assembly in controlled lipid environments. We find that membrane hydrophobic mismatch modulates oligomerization and assembly energetics, and 2D organization. Our experimental and theoretical frameworks reveal how membrane organization can emerge from Brownian diffusion and a minimal set of physical properties of the membrane constituents.
Topics: Membrane Proteins; Membranes; Biophysics; Protein Domains; Phospholipids
PubMed: 36450733
DOI: 10.1038/s41467-022-35202-8 -
FEBS Letters Jul 2022The membrane occupation and recognition nexus (MORN) motif was first defined in 2000, when it was identified in the junctophilin protein family. Dozens of studies have... (Review)
Review
The membrane occupation and recognition nexus (MORN) motif was first defined in 2000, when it was identified in the junctophilin protein family. Dozens of studies have been published ever since, mainly focusing on the function of a given MORN motif-containing protein in parasites, plants or animal cells. Proteins with MORN motifs are not only expressed in most animal and plant cell types, but also significantly differ in their intracellular localization, suggesting that the MORN motifs may fulfill multiple physiological functions. Recent studies have found that MORN motif-containing proteins junctophilin-1/2 and MORN3 play a role in cardiac hypertrophy, skeletal muscle fiber stability and cancer. Hence, MORN motif-containing proteins may be exploited to develop improved treatments for various pathological conditions, such as cardiovascular diseases. Here, we review current research on MORN motif-containing proteins in different organisms and provide both ideas and approaches for follow-up exploration of their functions and applications.
Topics: Animals; Cell Membrane; Membranes; Occupations; Protein Transport
PubMed: 35568981
DOI: 10.1002/1873-3468.14378