Membrane tension evolution and mechanical regulation of melittin-induced membrane poration

Membrane tension plays a crucial role in various fundamental cellular processes,with one notable example being the T cell-mediated elimination of tumor cells through perforin-induced membrane perforation by amplifying cellular force.However,the mechanisms governing the regulation of biomolecular activities at the cell interface by membrane tension remain elusive.In this study,we investigated the correlation between membrane tension and poration activity of melittin,a prototypical pore-forming peptide,using dynamic giant unilamellar vesicle leakage assays combined with flickering tension analysis,molecular dynamics simulations,and live cell assays.The results demonstrate that an increase in membrane tension enhances the activity of melittin,particularly near its critical pore-forming concentration.Moreover,peptide actions such as binding,insertion,and aggregation in the membrane further influence the evolution of membrane tension.Live cell experiments reveal that artificially enhancing membrane tension effectively enhances melittin’s ability to induce pore formation and disrupt membranes,resulting in up to a ten-fold increase in A549 cell mortality when exposed to a concentration of 2.0-μg·mL^(-1)melittin.Our findings elucidate the relationship between membrane tension and the mechanism of action as well as pore-forming efficiency of melittin,while providing a practical mechanical approach for regulating functional activity of molecules at the cell-membrane interface.

A numerical method to predict the membrane tension distribution of spreading cells based on the reconstruction of focal adhesions

Changes in membrane tension significantly affect the physiological functions of cells in various ways.However,directly measuring the spatial distribution of membrane tension remains an ongoing issue.In this study,an algorithm is proposed to determine the membrane tension inversely by executing a particle-based method and searching for the minimum deformation energy based on the cell images and focal adhesions.A standard spreading cell model is established using 3D reconstructions with images from structured illumination microscopy as the reference cell shape.The membrane tension distribution,forces across focal adhesions,and profile of the spread cell are obtained using this method,until the cell deformation energy function optimization converges.Qualitative and quantitative comparisons with previous experimental results validated the reliability of this method.The results show that in the standard spreading cell model,the membrane tension decreases from the bottom to the top of the membrane.This method can be applied to predict the membrane tension distribution of cells freely spreading into different shapes,which could improve the quantitative analysis of cellular membrane tension in various studies for cell mechanics.

Di-4-ANEPPDHQ probes the response of lipid packing to the membrane tension change in living cells

Membrane tension plays a significant role in many cellular processes including cell adhesion, migration and spreading. Despite the importance of membrane tension, it remains difficult to measure in vivo. Recently, the development of non-invasive fluorescent probes have made great progress, especially excitedstate deplanarization in molecular rotors has been applied to image membrane tension in living cells.Nevertheless, an intrinsic limitation of such kind of probe is that they depend on the lipid packing, and how the lipid packing responds to the membrane tension change remains unclear. Therefore, in this work,we used a polarity-sensitive membrane probe to investigate the possible response mechanism of lipid packing to the change of membrane tension that was regulated by osmotic shocks. The results showed that an increase in membrane tension could stretch the lipids apart with large displacements, and this change was not homogeneous on the whole membrane, instead, increase of membrane tension induced phase separation.

Regulation of the intermittent release of giant unilamellar vesicles under osmotic pressure

Osmotic pressure can break the fluid balance between intracellular and extracellular solutions.In hypo-osmotic so-lution,water molecules,which transfer into the cell and burst,are driven by the concentration difference of solute across the semi-permeable membrane.The complicated dynamic processes of intermittent bursts have been previously observed.However,the underlying physical mechanism has yet to be thoroughly explored and analyzed.Here,the intermittent re-lease of inclusion in giant unilamellar vesicles was investigated quantitatively,applying the combination of experimental and theoretical methods in the hypo-osmotic medium.Experimentally,we adopted a highly sensitive electron multiplying charge-coupled device to acquire intermittent dynamic images.Notably,the component of the vesicle phospholipids af-fected the stretch velocity,and the prepared solution of vesicles adjusted the release time.Theoretically,we chose equations and numerical simulations to quantify the dynamic process in phases and explored the influences of physical parameters such as bilayer permeability and solution viscosity on the process.It was concluded that the time taken to achieve the balance of giant unilamellar vesicles was highly dependent on the molecular structure of the lipid.The pore lifetime was strongly related to the internal solution environment of giant unilamellar vesicles.The vesicles prepared in viscous solution were able to visualize long-lived pores.Furthermore,the line tension was measured quantitatively by the release velocity of inclusion,which was of the same order of magnitude as the theoretical simulation.In all,the experimental values well matched the theoretical values.Our investigation clarified the physical regulatory mechanism of intermittent pore forma-tion and inclusion release,which provides an important reference for the development of novel technologies such as gene therapy based on transmembrane transport as well as controlled drug delivery based on liposomes.

On the gating of mechanosensitive channels by fluid shear stress

Mechanosensation is an important process in biological fluid-structure interaction. To understand the biophysics underlying mechanosensation, it is essential to quantify the correlation between membrane deformation, membrane tension, external fluid shear stress, and conformation of mechanosensitive (MS) channels. Smoothed dissipative particle dynamics (SDPD) simulations of vesicle/cell in three types of flow configurations are conducted to calculate the tension in lipid membrane due to fluid shear stress from the surrounding viscous flow. In combination with a simple continuum model for an MS channel, SDPD simulation results suggest that shearing adhered vesicles/cells is more effective to induce membrane tension sufficient to stretch MS channels open than a free shear flow or a constrictive channel flow. In addition, we incorporate the bilayer-cytoskeletal interaction in a two-component model to probe the effects of a cytoskeletal network on the gating of MS channels.

Shape analysis and optimization of airbag for space inflatable antenna

The characteristics of normal inflatable antennas are described in this paper.For its deficiency such as low stiffness,a new-style of rigid-flexible coupling inflatable antenna is introduced.The advantages and system-composition are presented.Airbag is an important component,and the shape and stress distribution of airbag is important for the whole structure.Thus,shape-state analysis is performed.The uniformity of constrained force at joint between airbag and rib will impact the state of joint,or even the deployment process.Therefore,a shape optimization of airbag is developed on the base of genetic algorithms,and the best shape of airbag is finally obtained.Therefore,the stress distribution of airbags will be uniformed and the antenna structure system will be more reliability.

How plants sense and respond to osmotic stress

Drought is one of the most serious abiotic stresses to land plants.Plants sense and respond to drought stress to survive under water deficiency.Scientists have studied how plants sense drought stress,or osmotic stress caused by drought,ever since Charles Darwin,and gradually obtained clues about osmotic stress sensing and signaling in plants.Osmotic stress is a physical stimulus that triggers many physiological changes at the cellular level,including changes in turgor,cell wall stiffness and integrity,membrane tension,and cell fluid volume,and plants may sense some of these stimuli and trigger downstream responses.In this review,we emphasized water potential and movements in organisms,compared putative signal inputs in cell wall-containing and cell wall-free organisms,prospected how plants sense changes in turgor,membrane tension,and cell fluid volume under osmotic stress according to advances in plants,animals,yeasts,and bacteria,summarized multilevel biochemical and physiological signal outputs,such as plasma membrane nanodomain formation,membrane water permeability,root hydrotropism,root halotropism,Casparian strip and suberin lamellae,and finally proposed a hypothesis that osmotic stress responses are likely to be a cocktail of signaling mediated by multiple osmosensors.We also discussed the core scientific questions,provided perspective about the future directions in this field,and highlighted the importance of robust and smart root systems and efficient source-sink allocations for generating future high-yield stress-resistant crops and plants.

Mechanisms of neuronal membrane sealing following mechanical trauma

Membrane integrity is crucial for maintaining the intricate signaling and chemically-isolated intracellular environment of neurons; disruption risks deleterious effects, such as unregulated ionic flux, neuronal apoptosis, and oxidative radical damage as observed in spinal cord injury and traumatic brain injury. This paper, in addition to a discussion of the current understanding of cellular tactics to seal membranes, describes two major factors involved in membrane repair. These are line tension, the hydrophobic attractive force between two lipid free-edges, and membrane tension, the rigidity of the lipid bilayer with respect to the tethered cortical cytoskeleton. Ca2~, a major mechanistic trigger for repair processes, increases following flux through a membrane injury site, and activates phospholipase enzymes, calpain-mediated cortical cytoskeletal proteolysis, protein kinase cascades, and lipid bilayer microdomain modification. The membrane tension appears to be largely modulated through vesicle dynamics, cytoskeletal organization, membrane curvature, and phospholipase manipulation. Dehydration of the phospholipid gap edge and modification of membrane packaging, as in temperature variation, experimentally impact line tension. Due to the time-sensitive nature of axonal sealing, increasing the efficacy of axolemmal sealing through therapeutic modification would be of great clinical value, to deter secondary neurodegenerative effects. Better therapeutic enhancement of membrane sealing requires a complete understanding of its intricate underlying neuronal mechanism.

An efficient numerical shape analysis for light weight membrane structures

The determination of initial equilibrium shapes is a common problem in research work and engineering applications related to membrane structures. Using a general structural analysis framework of the finite particle method （FPM）, this paper presents the first application of the FPM and a recently-developed membrane model to the shape analysis of light weight mem- branes. The FPM is rooted in vector mechanics and physical viewpoints. It discretizes the analyzed domain into a group of parti- cles linked by elements, and the motion of the free particles is directly described by Newton＇s second law while the constrained ones follow the prescribed paths. An efficient physical modeling procedure of handling geometric nonlinearity has been developed to evaluate the particle interaction forces. To achieve the equilibrium shape as fast as possible, an integral-form, explicit time integration scheme has been proposed for solving the equation of motion. The equilibrium shape can be obtained naturally without nonlinear iterative correction and global stiffness matrix integration. Two classical curved surfaces of tension membranes pro- duced under the uniform-stress condition are presented to verify the accuracy and efficiency of the proposed method.