Clathrin-mediated endocytosis (CME) is a key pathway for transporting cargo into cells via membrane vesicles; it plays an integral role in nutrient import, signal transduction, neurotransmission, and ...cellular entry of pathogens and drug-carrying nanoparticles. Because CME entails substantial local remodeling of the plasma membrane, the presence of membrane tension offers resistance to bending and hence, vesicle formation. Experiments show that in such high-tension conditions, actin dynamics is required to carry out CME successfully. In this study, we build on these pioneering experimental studies to provide fundamental mechanistic insights into the roles of two key endocytic proteins—namely, actin and BAR proteins—in driving vesicle formation in high membrane tension environment. Our study reveals an actin force-induced “snap-through instability” that triggers a rapid shape transition from a shallow invagination to a highly invaginated tubular structure. We show that the association of BAR proteins stabilizes vesicles and induces a milder instability. In addition, we present a rather counterintuitive role of BAR depolymerization in regulating the shape evolution of vesicles. We show that the dissociation of BAR proteins, supported by actin–BAR synergy, leads to considerable elongation and squeezing of vesicles. Going beyond the membrane geometry, we put forth a stress-based perspective for the onset of vesicle scission and predict the shapes and composition of detached vesicles. We present the snap-through transition and the high in-plane stress as possible explanations for the intriguing direct transformation of broad and shallow invaginations into detached vesicles in BAR mutant yeast cells.
Significance Biological cells are engaged in an incessant uptake of macromolecules for nutrition and inter- and intracellular communication; this entails significant local bending of the plasma membrane and formation of cargo-carrying vesicles executed by a designated set of membrane-deforming proteins. The energetic cost incurred in forming vesicles is directly related to the stressed state of the membrane and, hence, that of the cell. In this study, we reveal a protein-induced “snap-through instability” that offsets tension and drives vesicle growth during clathrin-mediated endocytosis, the main pathway for the transport of macromolecules into cells. Because these proteins (actin and BAR proteins) are involved in other interfacial rearrangements in cells, the predicted instability could be at play in cells at-large.
Cancer cell migration through narrow constrictions generates compressive stresses on the nucleus that deform it and cause rupture of nuclear membranes. Nuclear membrane rupture allows uncontrolled ...exchange between nuclear and cytoplasmic contents. Local tensile stresses can also cause nuclear deformations, but whether such deformations are accompanied by nuclear membrane rupture is unknown. Here we used a direct force probe to locally deform the nucleus by applying a transient tensile stress to the nuclear membrane. We found that a transient (∼0.2 s) deformation (∼1% projected area strain) in normal mammary epithelial cells (MCF-10A cells) was sufficient to cause rupture of the nuclear membrane. Nuclear membrane rupture scaled with the magnitude of nuclear deformation and the magnitude of applied tensile stress. Comparison of diffusive fluxes of nuclear probes between wild-type and lamin-depleted MCF-10A cells revealed that lamin A/C, but not lamin B2, protects the nuclear membranes against rupture from tensile stress. Our results suggest that transient nuclear deformations typically caused by local tensile stresses are sufficient to cause nuclear membrane rupture.
In this work electrospun amorphous polyvinylidene fluoride-co-hexafluoropropylene (PVDF-co-HFP) based separator is shown to have a superior gel electrolyte material suitable to the sodium-ion cell. ...The 16 wt.% polymer solution was electrospun under a voltage of 18 kV to get an amorphous electroactive β-phase structure. The amorphous β-phase is indexed by an X-ray diffractometer (XRD). The ionic conductivities, electrolyte uptakes, and linear sweep voltammetry (LSV) of the amorphous gel polymer electrolyte (AGPE) are investigated by saturating the separator membrane in a liquid electrolyte solution of 0.6 M sodium hexafluorophosphate (NaPF6) dissolved in ethylene carbonate (EC)/ propylene carbonate (PC) (1:1, vol.%). The AGPE displayed a high ionic conductivity of 1.28 × 10−3 S cm−1 and wide electrochemical stability up to 4.6 V vs Na/Na+ at room temperature. Further, the cells Na/AGPE/Na0.66Fe0.5Mn0.5O2 displayed an excellent cycling performance with little capacity loss.
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Membrane tension plays an inhibitory role in clathrin-mediated endocytosis (CME) by impeding the transition of flat plasma membrane to hemispherical clathrin-coated structures (CCSs). Membrane ...tension also impedes the transition of hemispherical domes to omega-shaped CCSs. However, CME is not completely halted in cells under high tension conditions. Here we find that epsin, a membrane bending protein which inserts its N-terminus H
helix into lipid bilayer, supports flat-to-dome transition of a CCS and stabilizes its curvature at high tension. This discovery is supported by molecular dynamic simulation of the epsin N-terminal homology (ENTH) domain that becomes more structured when embedded in a lipid bilayer. In addition, epsin has an intrinsically disordered protein (IDP) C-terminus domain which induces membrane curvature via steric repulsion. Insertion of H
helix into lipid bilayer is not sufficient for stable epsin recruitment. Epsin's binding to adaptor protein 2 and clathrin is critical for epsin's association with CCSs under high tension conditions, supporting the importance of multivalent interactions in CCSs. Together, our results support a model where the ENTH and unstructured IDP region of epsin have complementary roles to ensure CME initiation and CCS maturation are unimpeded under high tension environments.
To evaluate choroidal vascularity index (CVI) among normal subjects using image binarization of swept source optical coherence tomography (SS-OCT).
Four hundred and sixty eyes of 230 normal ...participants were included. Total circumscribed choroidal area, luminal area, stromal area (SA), and CVI were derived from SS-OCT scans using open-source software (ImageJ) with the modified Niblack method. Both CVI and subfoveal choroidal thickness (SFCT) were correlated with age, refractive error, intraocular pressure, and mean ocular perfusion pressure (MOPP) using mixed linear model analysis. Pearson's correlation coefficient was used to determine the relationship between age and each dependent factor. Analyses were performed using the SPSS software version 20.0 (IBM Corp., Armonk USA) and statistical significance was tested at 5%.
The mean age was 42.1 (±17.6) years. Mean SFCT was 307 ± 79 μm. Mean CVI was 66.80 (±3.8)%. There was statistically significant positive correlation between CVI and increasing age (
= 0.259,
< 0.0001) and statistically significant negative correlation between SFCT and age (
= -0.361,
< 0.0001). There was positive linear correlation between refractive error and CVI (
= 0.220,
< 0.0001) and negative correlation between SFCT and refractive error. There was no significant effect of MOPP on both CVI (
= 0.07) and SFCT (
= 0.7).
CVI and SFCT are significantly correlated with age and refractive error in normal Indian eyes.
The performance sensitivity of the solid‐state lithium cells to the synergistic interactions of the charge‐transport and mechanical properties of the electrolyte is well acknowledged in the ...literature, but the quantitative insights therein are very limited. Here, the charge‐transport and mechanical properties of a polymerized ionic‐liquid‐based solid electrolyte are reported. The transference number and diffusion coefficient of lithium in the concentrated solid electrolyte are measured as a function of concentration and stack pressure. The elastoplastic behavior of the electrolyte is quantified under compression, within a home‐made setup, to substantiate the impact of stack pressure on the stability of the Li/electrolyte interface in the symmetric lithium cells. The results spotlight the interaction between the concentration and thickness of the solid electrolyte and the stack pressure in determining the polarization and stability of the solid‐state lithium batteries during extended cycling.
This study quantifies the complex interaction among adjustable design parameters of a solid polymer electrolyte in determining the polarization and stability of a symmetric solid‐state Li cell made thereof. The charge‐transport and mechanical properties of the solid electrolyte are reported at different stack pressures and used for a comprehensive interpretation of the short‐ and long‐term performance of the cells.
AIM: To analyze choroidal parameters in eyes with diabetic macular edema (DME) treated with intravitreal Ozurdex.
PATIENTS AND METHODS: Twenty eyes of 14 patients were included in this prospective ...study. Optical coherence tomography images were obtained before and 8-10 weeks after intravitreal Ozurdex injection; binarized and subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI) were calculated.
RESULTS: Mean SFCT (treatment naïve; 242.22 ± 32.87 reduced to 218.10 ± 22.10, P = 0.158 and previously treated; 330.4 ± 56.72 reduced to 328.93 ± 50.55, P = 0.833) and mean CVI (treatment naïve; 0.64 ± 0.03 changed to 0.65 ± 0.04, P = 0.583 and previously treated; 0.65 ± 0.05 reduced to 0.64 ± 0.03, P = 0.208) showed no significant change.
CONCLUSION: Intravitreal Ozurdex showed no significant effects on SFCT and CVI in eyes with DME over short term. Larger studies with longer follow-up may allow a better understanding.
Mitochondria, the double membrane-walled powerhouses of the eukaryotic cell, are also the seats of synthesis of two critical yet prevalent nonbilayer-prone phospholipids, namely ...phosphatidylethanolamine (PE) and cardiolipin (CL). Besides their established biochemical roles in the regulation of partner protein function, PE and CL are also key protagonists in the biophysics of mitochondrial membrane remodeling and dynamics. In this review, we address lipid geometry and behavior at the single-molecule level as well as their intimate coupling to whole organelle morphology and remodeling during the concerted events of mitochondrial fission. We present evidence from recent experimental measurements ably supported and validated by computational modeling studies to support our notion that conical lipids play a catalytic as well as a structural role in mitochondrial fission.
•Mitochondria are enriched in nonbilayer-prone conical lipids, particularly PE and CL.•Redistribution of conical lipids by proteins facilitate membrane superconstriction.•Conical lipids likely also play a catalytic role in mitochondrial membrane fission.•CL breakdown to PA and DAG may regulate mitochondrial fission.•Studies of membrane mechanics by computational modeling can sort the roles of lipids and proteins in mitochondrial dynamics.
Bacteria and leukocytes employ donut-shaped transcellular holes in plasma membrane to cross the endothelial barrier. How these fused holes are regulated in a double-bilayer system is currently poorly ...understood. Here we use membrane physics to present a universal relationship that determines the geometry of the donut-shaped holes. Our study reveals that hole radius is determined by plasma membrane tension via a commonly used critical length scale
κ
/
λ
defined by flexural stiffness (
κ
) and in-plane tension (
λ
). This relationship suggests that the hole diameter increases with a reduction in membrane tension, a finding aligned with the experimental observations but in contrast with the main current model in the literature.
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