Scaling of lipid membrane rigidity with domain area fraction.
Ontology highlight
ABSTRACT:
SUBMITTER: Kelley EG
PROVIDER: S-EPMC8220873 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Lipid membranes are suggested as the primary target of amyloid aggregates. We study aggregates formed by a polyglutamine (polyQ) peptide, and their disruptive effect on lipid membranes. Using solution atomic force microscopy (AFM), we observe polyQ oligomers coexisting with short fibrils, which have a twisted morphology that likely corresponds to two intertwined oligomer strings. Fourier transform infrared spectroscopy reveals that the content of β-sheet enriched aggregates increases with incubation time. Using fluorescence microscopy, we find that exposure to polyQ aggregates results in deflated morphology of giant unilamellar vesicles. PolyQ aggregates induced membrane disruption is further substantiated by time-dependent calcein leakage from the interior to the exterior of lipid vesicles. Detailed structural and mechanical perturbations of lipid membranes are revealed by solution AFM. We find that membrane disruption by polyQ aggregates proceeds by a two-step process, involving partial and full disruption. In addition to height contrast, the resulting partially and fully disrupted bilayers have distinct rigidity and adhesion force properties compared to the intact bilayer. Specifically, the bilayer rigidity increases as the intact bilayer becomes partially and fully disrupted. Surprisingly, the adhesion force first decreases and then increases during the disruption process. By resolving individual fibrils deposited on bilayer surface, we show that both the length and the number of fibrils can increase with incubation time. Our results highlight that membrane disruption could be the molecular basis of polyQ aggregates induced cytotoxicity.
| S-EPMC4779675 | biostudies-literature
Project description:The sculpting of membranes into dynamic, curved shapes is central to intracellular cargo trafficking. Though the generation of membrane curvature during trafficking necessarily involves both lipids and membrane-associated proteins, current mechanistic views focus primarily on the formation of rigid cages and curved scaffolds by protein assemblies. Here we report on a different mechanism for the control of membrane deformation, unrelated to the imposition of predefined curvature, involving modulation of membrane material properties: Sar1, a GTPase that regulates vesicle trafficking from the endoplasmic reticulum, lowers the rigidity of the lipid bilayer membrane to which it binds. In vitro assays in which optically trapped microspheres create controlled membrane deformations revealed a monotonic decline in bending modulus as a function of Sar1 concentration, down to nearly zero rigidity, indicating a dramatic lowering of the energetic cost of curvature generation. This is the first demonstration that a vesicle trafficking protein lowers the rigidity of its target membrane, leading to a new conceptual framework for vesicle biogenesis.
| S-EPMC2931751 | biostudies-literature
Project description:Cellular life relies on membranes, which provide a resilient and adaptive cell boundary. Many essential processes depend upon the ease with which the membrane is able to deform and bend, features that can be characterized by the bending rigidity. Quantitative investigations of such mechanical properties of biological membranes have primarily been undertaken in solely lipid bilayers and frequently in the absence of buffers. In contrast, much less is known about the influence of integral membrane proteins on bending rigidity under physiological conditions. We focus on an exemplar member of the ubiquitous major facilitator superfamily of transporters and assess the influence of lactose permease on the bending rigidity of lipid bilayers. Fluctuation analysis of giant unilamellar vesicles (GUVs) is a useful means to measure bending rigidity. We find that using a hydrogel substrate produces GUVs that are well suited to fluctuation analysis. Moreover, the hydrogel method is amenable to both physiological salt concentrations and anionic lipids, which are important to mimic key aspects of the native lactose permease membrane. Varying the fraction of the anionic lipid in the lipid mixture DOPC/DOPE/DOPG allows us to assess the dependence of membrane bending rigidity on the topology and concentration of an integral membrane protein in the lipid bilayer of GUVs. The bending rigidity gradually increases with the incorporation of lactose permease, but there is no further increase with greater amounts of the protein in the membrane.
| S-EPMC8456183 | biostudies-literature
Project description:Thermal fluctuations in cell membranes manifest as an excess area ([Formula: see text]) which governs a multitude of physical process at the sub-micron scale. We present a theoretical framework, based on an in silico tether pulling method, which may be used to reliably estimate [Formula: see text] in live cells. We perform our simulations in two different thermodynamic ensembles: (i) the constant projected area and (ii) the constant frame tension ensembles and show the equivalence of our results in the two. The tether forces estimated from our simulations compare well with our experimental measurements for tethers extracted from ruptured GUVs and HeLa cells. We demonstrate the significance and validity of our method by showing that all our calculations performed in the initial tether formation regime (i.e. when the length of the tether is comparable to its radius) along with experiments of tether extraction in 15 different cell types collapse onto two unified scaling relationships mapping tether force, tether radius, bending stiffness ?, and membrane tension ?. We show that [Formula: see text] is an important determinant of the radius of the extracted tether, which is equal to the characteristic length [Formula: see text] for [Formula: see text], and is equal to [Formula: see text] for [Formula: see text]. We also find that the estimated excess area follows a linear scaling behavior that only depends on the true value of [Formula: see text] for the membrane, based on which we propose a self-consistent technique to estimate the range of excess membrane areas in a cell.
| S-EPMC5832653 | biostudies-literature
Project description: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.
| S-EPMC8766614 | biostudies-literature
Project description:X-ray and neutron diffraction studies of a binary lipid membrane demonstrate that halothane at physiological concentrations produces a pronounced redistribution of lipids between domains of different lipid types identified by different lamellar d-spacings and isotope composition. In contrast, dichlorohexafluorocyclobutane (F6), a halogenated nonanesthetic, does not produce such significant effects. These findings demonstrate a specific effect of inhalational anesthetics on mixing phase equilibria of a lipid mixture.
| S-EPMC3302933 | biostudies-literature
Project description:We argue that membrane viscosity, ?(m), plays a prominent role in the thermal fluctuation dynamics of micron-scale lipid domains. A theoretical expression is presented for the timescales of domain shape relaxation, which reduces to the well-known ?(m) = 0 result of Stone and McConnell in the limit of large domain sizes. Experimental measurements of domain dynamics on the surface of ternary phospholipid and cholesterol vesicles confirm the theoretical results and suggest domain flicker spectroscopy as a convenient means to simultaneously measure both the line tension, ?, and the membrane viscosity, ?(m), governing the behavior of individual lipid domains.
| S-EPMC2941019 | biostudies-literature
Project description:Desmogleins (Dsgs) are cadherin family adhesion molecules essential for epidermal integrity. Previous studies have shown that desmogleins associate with lipid rafts, but the significance of this association was not clear. Here, we report that the desmoglein transmembrane domain (TMD) is the primary determinant of raft association. Further, we identify a novel mutation in the DSG1 TMD (G562R) that causes severe dermatitis, multiple allergies, and metabolic wasting syndrome. Molecular modeling predicts that this G-to-R mutation shortens the DSG1 TMD, and experiments directly demonstrate that this mutation compromises both lipid raft association and desmosome incorporation. Finally, cryo-electron tomography indicates that the lipid bilayer within the desmosome is ?10% thicker than adjacent regions of the plasma membrane. These findings suggest that differences in bilayer thickness influence the organization of adhesion molecules within the epithelial plasma membrane, with cadherin TMDs recruited to the desmosome via the establishment of a specialized mesoscale lipid raft-like membrane domain.
| S-EPMC6724694 | biostudies-literature
Project description:The outer membrane of Gram-negative bacteria is an asymmetric membrane with lipopolysaccharides on the external leaflet and phospholipids on the periplasmic leaflet. This outer membrane contains mainly β-barrel transmembrane proteins and lipidated periplasmic proteins (lipoproteins). The multisubunit protein β-barrel assembly machine (BAM) catalyzes the insertion and folding of the β-barrel proteins into this membrane. In Escherichia coli, the BAM complex consists of five subunits, a core transmembrane β-barrel with a long periplasmic domain (BamA) and four lipoproteins (BamB/C/D/E). The BamA periplasmic domain is composed of five globular subdomains in tandem called POTRA motifs that are key to BAM complex formation and interaction with the substrate β-barrel proteins. The BAM complex is believed to undergo conformational cycling while facilitating insertion of client proteins into the outer membrane. Reports describing variable conformations and dynamics of the periplasmic POTRA domain have been published. Therefore, elucidation of the conformational dynamics of the POTRA domain in full-length BamA is important to understand the function of this molecular complex. Using molecular dynamics simulations, we present evidence that the conformational flexibility of the POTRA domain is modulated by binding to the periplasmic surface of a native lipid membrane. Furthermore, membrane binding of the POTRA domain is compatible with both BamB and BamD binding, suggesting that conformational selection of different POTRA domain conformations may be involved in the mechanism of BAM-facilitated insertion of outer membrane β-barrel proteins.
| S-EPMC4919588 | biostudies-literature
Project description:Bacterial proteins with MCE domains were first described as being important for Mammalian Cell Entry. More recent evidence suggests they are components of lipid ABC transporters. In Escherichia coli, the single-domain protein MlaD is known to be part of an inner membrane transporter that is important for maintenance of outer membrane lipid asymmetry. Here we describe two multi MCE domain-containing proteins in Escherichia coli, PqiB and YebT, the latter of which is an orthologue of MAM-7 that was previously reported to be an outer membrane protein. We show that all three MCE domain-containing proteins localise to the inner membrane. Bioinformatic analyses revealed that MCE domains are widely distributed across bacterial phyla but multi MCE domain-containing proteins evolved in Proteobacteria from single-domain proteins. Mutants defective in mlaD, pqiAB and yebST were shown to have distinct but partially overlapping phenotypes, but the primary functions of PqiB and YebT differ from MlaD. Complementing our previous findings that all three proteins bind phospholipids, results presented here indicate that multi-domain proteins evolved in Proteobacteria for specific functions in maintaining cell envelope homeostasis.
| S-EPMC5561183 | biostudies-literature