Effect of pressure profile of shock waves on lipid membrane deformation.
Ontology highlight
ABSTRACT:
SUBMITTER: Kfoury R
PROVIDER: S-EPMC6383940 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Pex11p family proteins are key players in peroxisomal fission, but their molecular mechanisms remains mostly unknown. In the present study, overexpression of Pex11pβ caused substantial vesiculation of peroxisomes in mammalian cells. This vesicle formation was dependent on dynamin-like protein 1 (DLP1) and mitochondrial fission factor (Mff), as knockdown of these proteins diminished peroxisomal fission after Pex11pβ overexpression. The fission-deficient peroxisomes exhibited an elongated morphology, and peroxisomal marker proteins, such as Pex14p or matrix proteins harboring peroxisomal targeting signal 1, were discernible in a segmented staining pattern, like beads on a string. Endogenous Pex11pβ was also distributed a striped pattern, but which was not coincide with Pex14p and PTS1 matrix proteins. Altered morphology of the lipid membrane was observed when recombinant Pex11p proteins were introduced into proteo-liposomes. Constriction of proteo-liposomes was observed under confocal microscopy and electron microscopy, and the reconstituted Pex11pβ protein localized to the membrane constriction site. Introducing point mutations into the N-terminal amphiphathic helix of Pex11pβ strongly reduced peroxisomal fission, and decreased the oligomer formation. These results suggest that Pex11p contributes to the morphogenesis of the peroxisomal membrane, which is required for subsequent fission by DLP1.
| S-EPMC4467191 | biostudies-literature
Project description:Cellular membranes are, in general, impermeable to macromolecules (herein referred to as macrodrugs, e.g., recombinant protein, expression plasmids, or mRNA), which is a major barrier for clinical translation of macrodrug-based therapies. Encapsulation of macromolecules in lipid nanoparticles (LNPs) can protect the therapeutic agent during transport through the body and facilitate the intracellular delivery via a fusion-based pathway. Furthermore, designing LNPs responsive to stimuli can make their delivery more localized, thus limiting the side effects. However, the principles and criteria for designing such nanoparticles remain unclear. We show that the thermodynamic state of the lipid membrane of the nanoparticle is a key design principle for acoustically responsive fusogenic nanoparticles. We have optimized a cationic LNP (designated LNPLH) with two different phase transitions near physiological conditions for delivering mRNA. A bicistronic mRNA encoding a single domain intracellular antibody fragment and green fluorescent protein (GFP) was introduced into a range of human cancer cell types using LNPLH, and the protein expression was measured via fluorescence corresponding to the GFP expression. The LNPLH/mRNA complex demonstrated low toxicity and high delivery, which was significantly enhanced when the transfection occurred in the presence of acoustic shock waves. The results suggest that the thermodynamic state of LNPs provides an important criterion for stimulus responsive fusogenic nanoparticles to deliver macrodrugs to the inside of cells.
| S-EPMC6602409 | biostudies-literature
Project description:In this paper, an initial pressure adjustable explosion vessel was developed, and the effect of negative pressure, positive pressure (0.2-1.8 atm) different initial ambient pressure on the explosive shock wave generated by the explosion of explosives was studied. The relationships between the specific impulse, shock wave velocity, the amount of explosive gas products and the ambient pressure were analyzed for different initial pressure environments. It was found that: the overpressure of the blast shock wave decreases with the initial ambient pressure of the explosion, and there exists a negative pressure environment with a dramatic pressure decrease near 0.6 atm, defined as the super-sensitive negative pressure Pcr. The propagation velocity of an explosive wave increases with a decrease in the ambient pressure, and the propagation velocity at a pressure of 1.8 atm is four times less than the velocity at a pressure of 0.2 atm. The production of explosive gas products did not change. The greater the initial pressure of the environment where the explosive is located, the smaller the ratio of the gas generated by the explosion to the initial force gas in the explosion vessel is, and the greater the impact on the propagation of shock waves is. The maximum attenuation of the first specific impulse i1 is 72.97% and the maximum attenuation of the second specific impulse i2 is 72.39%. The experiments provide reference data for high-altitude military confrontation, high-altitude weapons and ammunition development, and deep-earth protection engineering.
| S-EPMC9399105 | biostudies-literature
Project description:Background Obesity became a worldwide public health problem and its treatment presents a strict relationship with skin flaccidity, for which the development of non-invasive therapies is an emerging field. Objective This study aims to evaluate the physiological response of the skin tissue of individuals with obesity with flaccidity to the physiological stimulus of shockwave therapy (ESWT). Methods This is a comparative intervention study based on histological and immunohistochemical analyses of a set of samples of skin tissue of women with Grade II obesity who achieved a 10 percent preoperative weight loss before bariatric surgery and complaints of skin flaccidity, subjected to the ESWT treatment. A total of seven sessions were carried out in the abdominal region on the left side, and the collateral side was used as control; the biological material was collected at the moment of the bariatric surgery. Hematoxylin and Eosin, Masson’s trichrome, Picrosirius Red and the markers for immunohistochemical were used for the morphological evaluation. Results Fourteen women were included in the research. The results demonstrated that the tissue which underwent the ESWT intervention presented significant increases of fibroblast cells (p<0.0001) and collagen fibers Type I and II (p<0.0002). In the significant expressions of the markers FGF1, FGF2, FGFR1 were identified in the exposed side (p<0.0002, 0.0017, <0.0001, respectively) as well as a significantly higher expression of Ki67 marker of cell proliferation (p<0.0002). Conclusion ESWT was associated with a significant increase of cell proliferation and collagen expression in flaccid skin of individuals who achieved weight loss before bariatric surgery.
| S-EPMC9586529 | biostudies-literature
Project description:Power grids, road maps, and river streams are examples of infrastructural networks which are highly vulnerable to external perturbations. An abrupt local change of load (voltage, traffic density, or water level) might propagate in a cascading way and affect a significant fraction of the network. Almost discontinuous perturbations can be modeled by shock waves which can eventually interfere constructively and endanger the normal functionality of the infrastructure. We study their dynamics by solving the Burgers equation under random perturbations on several real and artificial directed graphs. Even for graphs with a narrow distribution of node properties (e.g., degree or betweenness), a steady state is reached exhibiting a heterogeneous load distribution, having a difference of one order of magnitude between the highest and average loads. Unexpectedly we find for the European power grid and for finite Watts-Strogatz networks a broad pronounced bimodal distribution for the loads. To identify the most vulnerable nodes, we introduce the concept of node-basin size, a purely topological property which we show to be strongly correlated to the average load of a node.
| S-EPMC4018611 | biostudies-literature
Project description:Supported lipid bilayers have proven effective as model membranes for investigating biophysical processes and in development of sensor and array technologies. The ability to modify lipid bilayers after their formation and in situ could greatly advance membrane technologies, but is difficult via current state-of-the-art technologies. Here we demonstrate a novel method that allows the controlled post-formation processing and modification of complex supported lipid bilayer arrangements, under aqueous conditions. We exploit the destabilization effect of lipopolysaccharide, an amphiphilic biomolecule, interacting with lipid bilayers to generate voids that can be backfilled to introduce desired membrane components. We further demonstrate that when used in combination with a single, traditional soft lithography process, it is possible to generate hierarchically-organized membrane domains and microscale 2-D array patterns of domains. Significantly, this technique can be used to repeatedly modify membranes allowing iterative control over membrane composition. This approach expands our toolkit for functional membrane design, with potential applications for enhanced materials templating, biosensing and investigating lipid-membrane processes.
| S-EPMC4444833 | biostudies-literature
Project description:We have simulated effects of a shock wave in water that would result from the collapse of a cavitation bubble on binding in model complexes. We have considered a benzene dimer, a pair of uracil molecules, a complex of fragments of the X-linked inhibitor of apoptosis and caspase-9, and a fragment of c-Myc oncoprotein in binding with its dimerization partner Max. The effect of the shock waves was simulated by adding a momentum to a slab of solvent water molecules and observing the system as the slab moved and caused changes. In the cases of the small molecular pairs, the passage of the shock waves lead to dissociation of the complexes. The behavior of the protein systems was more complex, yet significant disruption of the binding and geometry was also observed. In all the cases, the effects did not occur during the immediate impact of the high-momentum solvent molecules, but rather during the expansion of the compressed system that followed the passage of the waves. The rationale of the studies was in attempting to understand the strong effects that irradiation with a low-intensity ultrasound can have on biomolecular systems, because such ultrasound irradiation can cause cavitation bubbles to be produced and collapse, thus leading to local shock wave generation. The long-term objective is to contribute to future design of synergetic ultrasound and chemical drug strategy of protein inhibition.
| S-EPMC4230379 | biostudies-literature
Project description:BackgroundYoganidra is a systematic method of promoting a state of complete physical, mental, and emotional relaxation. It is a safe, inexpensive, and very effective method of management of hypertension when used along with standard pharmacological therapy. This study aims to assess the effect of yoganidra on blood pressure (both systolic blood pressure (SBP) and diastolic blood pressure (DBP)), Hs-CRP, and lipid profile of hypertensive subjects at the time of enrollment (subjects that are hypertensive at the time of enrollment).MethodsBoth treated and untreated subjects (n = 74) with hypertension (blood pressure ≥140/90 mmHg) and age between 35 and 70 years were included in this study after obtaining ICMR-NIN-IEC approval and written informed consent from all subjects. Subjects with critical illness and/or psychological disturbances were excluded from this study. The subjects in the experimental group (n = 31) practiced yoganidra for 45 minutes daily for 12 weeks under strict supervision. There was no intervention in the control group (n = 43). Weekly blood pressure was recorded in the experimental group, whereas it was performed at baseline and at endpoint for control groups. Hs-CRP and lipid profile were estimated at baseline and endpoint for both the groups.ResultsA significant reduction in mean SBP from 142.9 mm Hg (SD ± 16.46) to 118.68 mm Hg (SD ± 9.21; p value 0.0001) and DBP from 89.84 mm Hg (SD ± 10.42) to 77.03 mm Hg (SD ± 6.47: p value 0.0001) was observed among the experimental group after 12 weeks of yoganidra practice when compared with the control group. A significant reduction in mean Hs-CRP (2.21 ± 1.49 to 1.06 ± 0.82 mg/L, p < 0.001 ∗∗∗ ) was observed among the experimental group. There were no significant differences between triglycerides and total cholesterol levels, whereas LDL-C and HDL-C showed a trend of improvement in the experimental group after intervention.ConclusionsIn this pilot study, we observed a significant reduction in blood pressure and Hs-CRP in the yoganidra group compared with the control group. There were no significant side effects observed in the intervention group during the study period.
| S-EPMC8739171 | biostudies-literature
Project description:Lipid bilayers represent a fascinating class of biomaterials whose properties are altered by changes in pressure or temperature. Functions of cellular membranes can be affected by nonspecific lipid-protein interactions that depend on bilayer material properties. Here we address the changes in lipid bilayer structure induced by external pressure. Solid-state ²H NMR spectroscopy of phospholipid bilayers under osmotic stress allows structural fluctuations and deformation of membranes to be investigated. We highlight the results from NMR experiments utilizing pressure-based force techniques that control membrane structure and tension. Our ²H NMR results using both dehydration pressure (low water activity) and osmotic pressure (poly(ethylene glycol) as osmolyte) show that the segmental order parameters (S(CD)) of DMPC approach very large values of ? 0.35 in the liquid-crystalline state. The two stresses are thermodynamically equivalent, because the change in chemical potential when transferring water from the interlamellar space to the bulk water phase corresponds to the induced pressure. This theoretical equivalence is experimentally revealed by considering the solid-state ²H NMR spectrometer as a virtual osmometer. Moreover, we extend this approach to include the correspondence between osmotic pressure and hydrostatic pressure. Our results establish the magnitude of the pressures that lead to significant bilayer deformation including changes in area per lipid and volumetric bilayer thickness. We find that appreciable bilayer structural changes occur with osmotic pressures in the range of 10-100 atm or lower. This research demonstrates the applicability of solid-state ²H NMR spectroscopy together with bilayer stress techniques for investigating the mechanism of pressure sensitivity of membrane proteins.
| S-EPMC3010004 | biostudies-literature
Project description:Lipid rafts are thought to be key organizers of membrane-protein complexes in cells. Many proteins that interact with rafts have bulky polymeric components such as intrinsically disordered protein domains and polysaccharide chains. Therefore, understanding the interaction between membrane domains and membrane-bound polymers provides insights into the roles rafts play in cells. Multiple studies have demonstrated that high concentrations of membrane-bound polymeric domains create significant lateral steric pressure at membrane surfaces. Furthermore, our recent work has shown that lateral steric pressure at membrane surfaces opposes the assembly of membrane domains. Building on these findings, here we report that membrane-bound polymers are potent suppressors of membrane phase separation, which can destabilize lipid domains with substantially greater efficiency than globular domains such as membrane-bound proteins. Specifically, we created giant vesicles with a ternary lipid composition, which separated into coexisting liquid ordered and disordered phases. Lipids with saturated tails and poly(ethylene glycol) (PEG) chains conjugated to their head groups were included at increasing molar concentrations. When these lipids were sparse on the membrane surface they partitioned to the liquid ordered phase. However, as they became more concentrated, the fraction of GUVs that were phase-separated decreased dramatically, ultimately yielding a population of homogeneous membrane vesicles. Experiments and physical modeling using compositions of increasing PEG molecular weight and lipid miscibility phase transition temperature demonstrate that longer polymers are the most efficient suppressors of membrane phase separation when the energetic barrier to lipid mixing is low. In contrast, as the miscibility transition temperature increases, longer polymers are more readily driven out of domains by the increased steric pressure. Therefore, the concentration of shorter polymers required to suppress phase separation decreases relative to longer polymers. Collectively, our results demonstrate that crowded, membrane-bound polymers are highly efficient suppressors of phase separation and suggest that the ability of lipid domains to resist steric pressure depends on both their lipid composition and the size and concentration of the membrane-bound polymers they incorporate.
| S-EPMC4914385 | biostudies-literature