Membrane Wrapping Research Articles

Differential cellular uptake and trafficking of nanoplastics in two hemocyte subpopulations of mussels Perna viridis

Nanoplastics (NPs) could be ingested by bivalves and translocated to their hemocytes, which played critical roles in immune-defense. In this study, highly fluorescent aggregation-induced emission nanoplastics (AIE-NPs) of two sizes (50 nm and 200 nm) were utilized to explore the dynamic systems of cellular uptake, intracellular trafficking, and ultimate localization in the granulocyte and agranulocyte subpopulations of hemocytes in the green mussels Perna viridis. We firstly revealed their differential cellular uptake and trafficking of nanoplastics in two hemocyte subpopulation systems. Specifically, agranulocytes performed relatively faster uptake rate for nanoplastics of two sizes, whereas granulocytes had about tenfold higher accumulation capacity. Unexpectedly, there was little removal of nanoplastics in the two subpopulation systems, and such persistence probably could trigger more severe cytotoxicity. Considerable amounts of 200 nm NPs without plasma membrane wrapping were present in the agranulocytes, which may be related to their unique caveolae-mediated uptake pathway. We further demonstrated that the internalized NPs accelerated the differentiation of agranulocytes into granulocytes with higher immunoreactivity, which may be a crucial detoxification mechanism. Our results highlighted the size-driven fate of NPs in different subpopulations of mussel hemocytes, contributing to a more comprehensive understanding of the toxicity of NPs to aquatic organisms.

Oligodendrocytes: Myelination, Plasticity, and Axonal Support.

The myelination of axons has evolved to enable fast and efficient transduction of electrical signals in the vertebrate nervous system. Acting as an electric insulator, the myelin sheath is a multilamellar membrane structure around axonal segments generated by the spiral wrapping and subsequent compaction of oligodendroglial plasma membranes. These oligodendrocytes are metabolically active and remain functionally connected to the subjacent axon via cytoplasmic-rich myelinic channels for movement of metabolites and macromolecules to and from the internodal periaxonal space under the myelin sheath. Increasing evidence indicates that oligodendrocyte numbers, specifically in the forebrain, and myelin as a dynamic cellular compartment can both respond to physiological demands, collectively referred to as adaptive myelination. This review summarizes our current understanding of how myelin is generated, how its function is dynamically regulated, and how oligodendrocytes support the long-term integrity of myelinated axons.

Membrane fission via transmembrane contact

Division of intracellular organelles often correlates with additional membrane wrapping, e.g., by the endoplasmic reticulum or the outer mitochondrial membrane. Such wrapping plays a vital role in proteome and lipidome organization. However, how an extra membrane impacts the mechanics of the division has not been investigated. Here we combine fluorescence and cryo-electron microscopy experiments with self-consistent field theory to explore the stress-induced instabilities imposed by membrane wrapping in a simple double-membrane tubular system. We find that, at physiologically relevant conditions, the outer membrane facilitates an alternative pathway for the inner-tube fission through the formation of a transient contact (hemi-fusion) between both membranes. A detailed molecular theory of the fission pathways in the double membrane system reveals the topological complexity of the process, resulting both in leaky and leakless intermediates, with energies and topologies predicting physiological events.

Development of a bottom-up coarse-grained model for interactions of lipids with TiO nanoparticles.

Understanding interactions of inorganic nanoparticles with biomolecules is important in many biotechnology, nanomedicine, and toxicological research, however, the size of typical nanoparticles makes their direct modeling by atomistic simulations unfeasible. Here, we present a bottom-up coarse-graining approach for modeling titanium dioxide (TiO ) nanomaterials in contact with phospholipids that uses the inverse Monte Carlo method to optimize the effective interactions from the structural data obtained in small-scale all-atom simulations of TiO surfaces with lipids in aqueous solution. The resulting coarse-grained models are able to accurately reproduce the structural details of lipid adsorption on different titania surfaces without the use of an explicit solvent, enabling significant computational resource savings and favorable scaling. Our coarse-grained simulations show that small spherical TiO nanoparticles ( nm) can only be partially wrapped by a lipid bilayer with phosphoethanolamine headgroups, however, the lipid adsorption increases with the radius of the nanoparticle. The current approach can be used to study the effect of the size and shape of TiO nanoparticles on their interactions with cell membrane lipids, which can be a determining factor in membrane wrapping as well as the recently discovered phenomenon of nanoquarantining, which involves the formation of layered nanomaterial-lipid structures.

Generation of a Hydrophobic Protrusion on Nanoparticles to Improve the Membrane‐Anchoring Ability and Cellular Internalization

AbstractControlling the nanoparticle‐cell membrane interaction to achieve easy and fast membrane anchoring and cellular internalization is of great importance in a variety of biomedical applications. Here we report a simple and versatile strategy to maneuver the nanoparticle‐cell membrane interaction by creating a tunable hydrophobic protrusion on Janus particles through swelling‐induced symmetry breaking. When the Janus particle contacts cell membrane, the protrusion will induce membrane wrapping, leading the particles to docking to the membrane, followed by drawing the whole particles into the cell. The efficiencies of both membrane anchoring and cellular internalization can be promoted by optimizing the size of the protrusion. In vitro, the Janus particles can quickly anchor to the cell membrane in 1 h and be internalized within 24 h, regardless of the types of cells involved. In vivo, the Janus particles can effectively anchor to the brain and skin tissues to provide a high retention in these tissues after intracerebroventricular, intrahippocampal, or subcutaneous injection. This strategy involving the creation of a hydrophobic protrusion on Janus particles to tune the cell‐membrane interaction holds great potential in nanoparticle‐based biomedical applications.

Effective cell membrane tension protects red blood cells against malaria invasion.

A critical step in how malaria parasites invade red blood cells (RBCs) is the wrapping of the membrane around the egg-shaped merozoites. Recent experiments have revealed that RBCs can be protected from malaria invasion by high membrane tension. While cellular and biochemical aspects of parasite actomyosin motor forces during the malaria invasion have been well studied, the important role of the biophysical forces induced by the RBC membrane-cytoskeleton composite has not yet been fully understood. In this study, we use a theoretical model for lipid bilayer mechanics, cytoskeleton deformation, and membrane-merozoite interactions to systematically investigate the influence of effective RBC membrane tension, which includes contributions from the lipid bilayer tension, spontaneous tension, interfacial tension, and the resistance of cytoskeleton against shear deformation on the progression of membrane wrapping during the process of malaria invasion. Our model reveals that this effective membrane tension creates a wrapping energy barrier for a complete merozoite entry. We calculate the tension threshold required to impede the malaria invasion. We find that the tension threshold is a nonmonotonic function of spontaneous tension and undergoes a sharp transition from large to small values as the magnitude of interfacial tension increases. We also predict that the physical properties of the RBC cytoskeleton layer-particularly the resting length of the cytoskeleton-play key roles in specifying the degree of the membrane wrapping. We also found that the shear energy of cytoskeleton deformation diverges at the full wrapping state, suggesting the local disassembly of the cytoskeleton is required to complete the merozoite entry. Additionally, using our theoretical framework, we predict the landscape of myosin-mediated forces and the physical properties of the RBC membrane in regulating successful malaria invasion. Our findings on the crucial role of RBC membrane tension in inhibiting malaria invasion can have implications for developing novel antimalarial therapeutic or vaccine-based strategies.

Fresh human amniotic membrane wrapping promotes peripheral nerve regeneration in PGA-collagen tubes.

An artificial nerve conduit can interpose the peripheral nerve defect without donor site morbidity. However, treatment outcomes are often unsatisfactory. Human amniotic membrane (HAM) wrapping has been reported to promote peripheral nerve regeneration. We evaluated the effects of a combined application of fresh HAM wrapping and a polyglycolic acid tube filled with collagen (PGA-c) in a rat sciatic nerve 8-mm defect model. The rats were divided into three groups: (1) the PGA-c group (n = 5), in which the gap was interposed with the PGA-c; (2) the PGA-c/HAM group (n = 5), in which the gap was interposed with the PGA-c bridge, then HAM (14 × 7 mm) was wrapped around it; and (3) the Sham group (n = 5). Walking-Track recovery, electromyographic recovery, and histological recovery of the regenerated nerve were evaluated at 12 weeks postoperatively. Compared to the PGA-c group, the PGA-c/HAM group showed significantly better recovery in terminal latency (3.4 ± 0.31 ms vs. 6.6 ± 0.72 ms, p < 0.001), compound muscle action potential (0.19 ± 0.025 mV vs. 0.072 ± 0.027 mV, p < 0.01), myelinated axon perimeter (15 ± 1.3 μm vs. 8.7 ± 0.63 μm, p < 0.01), and g-ratio (0.69 ± 0.0089 vs. 0.78 ± 0.014, p < 0.001). This combined application highly promotes peripheral nerve regeneration and may be more useful than PGA-c alone.

An analytical model describing the mechanics of erythrocyte membrane wrapping during active invasion of a plasmodium falciparum merozoite

The invasion of a merozoite into an erythrocyte by membrane wrapping is a hallmark of malaria pathogenesis. The invasion involves biomechanical interactions whereby the merozoite exerts actomyosin-based forces to push itself into and through the erythrocyte membrane while concurrently inducing biochemical damage to the erythrocyte membrane. Whereas the biochemical damage process has been investigated, the detailed mechanistic understanding of the invasion mechanics remains limited. Thus, the current study aimed to develop a mathematical model describing the mechanical factors involved in the merozoite invasion into an erythrocyte and explore the invasion mechanics.A shell theory model was developed comprising constitutive, equilibrium and governing equations of the deformable erythrocyte membrane to predict membrane mechanics during the wrapping of an entire non-deformable ellipsoidal merozoite. Predicted parameters include principal erythrocyte membrane deformations and stresses, wrapping and indentation forces, and indentation work. The numerical investigations considered two limits for the erythrocyte membrane deformation during wrapping (4% and 51% areal strain) and erythrocyte membrane phosphorylation (decrease of membrane elastic modulus from 1 to 0.5 kPa).For an intact erythrocyte, the maximum indentation force was 1 and 8.5 pN, and the indentation work was 1.92 × 10−18 and 1.40 × 10−17 J for 4% and 51% areal membrane strain. Phosphorylation damage in the erythrocyte membrane reduced the required indentation work by 50% to 0.97 × 10−18 and 0.70 × 10−17 J for 4% and 51% areal strain.The current study demonstrated the developed model's feasibility to provide new knowledge on the physical mechanisms of the merozoite invasion process that contribute to the invasion efficiency towards the discovery of new invasion-blocking anti-malaria drugs.

Direct Piercing of Ag Nanowires into Living Macrophages: Implications for Nanotoxicity

High aspect ratio nanomaterials, such as nanowires, are known to exhibit unique properties and have a wide range of applications owing to their geometry and small diameters. Prior work has indicated that silver nanowires (AgNWs, more than 15 μm long) could lead to frustrated phagocytosis in lung macrophages, whose characteristics differ from those among the micro- and macro-wires with the same chemical compositions. This work unveils whether other pathways occur upon exposure of living cells to AgNWs. Using high-resolution laser scanning confocal microscopy, the precise locations of AgNWs with respect to cells can be visualized upon exposure of a macrophage cell line, NR8383 cells, to AgNWs. Cellular membranes and intracellular components, such as actin, are also tagged to allow direct and detailed visualization of cellular components with respect to AgNWs during exposures. Direct piercing of AgNWs into cells was captured, where a portion of wires was poked into a cell without significant structural perturbation of its local surroundings. While AgNWs were predicted to be able to poke through the cell membrane from computation studies, direct piercing has not been experimentally observed until the present work. Other scenarios include frustrated phagocytosis and failed attempts by AgNWs to pierce due to the membrane wrapping of the invading portion of the AgNWs resisting their entry. The comprehensive studies of AgNW–cell interactions are of fundamental importance in understanding nanocytotoxicity and nanotoxicity. The knowledge gained shall facilitate the development of preventive measures for the potential adversarial impacts of nanowires on the environment and human health, thus enabling broader applications of nanomaterials.

Thermal-controlled cellular uptake of "hot" nanoparticles.

Nanoparticles (NPs) have shown immense potential in the field of biomedical applications, particularly in NP-based photothermal therapy, which offers a remote-controlled approach to achieve precise temperature control for site-specific heating and sub-cellular tumor treatment. However, the molecular mechanisms underlying related cellular activities, such as the cellular uptake behavior of irradiated NPs in photothermal effects, remain elusive. In this study, we conducted a thorough investigation of the interaction between an irradiated NP with elevated temperature (ranging from 270 to 360 K) and a model bilayer membrane composed of DPPC or DOPC using nonequilibrium coarse-grained molecular dynamics simulations with the implicit-solvent Dry Martini force field. We observe that the interaction between a "hot" NP and a membrane is thermally regulated. In addition, the wrapping of membranes around NPs exhibits a strong dependence on the temperature of the irradiated NP, demonstrating a step-like change in behavior. This membrane wrapping effect is attributed to the heat conduction between NPs and membrane lipids, which occurs almost simultaneously with the membrane deformation and wrapping of NPs during the NP-membrane interaction process. Especially, during the process of heat conduction, a gel-to-fluid phase transition of the membrane may occur, which plays a crucial role in determining the deformation behavior of the membrane. Moreover, it is found that the membrane lipids in the two leaflets exhibit obvious and asymmetric molecular-level responses to heat flux, characterized by significant changes in packing states (e.g., the order parameter of lipid tails and area per lipid) and possible interdigitation between lipids. Furthermore, the thermal-controlled wrapping effect is tightly linked to the properties of NPs (e.g., size, NP-lipid affinity) and lipid species. Our findings are valuable for comprehending the thermal-regulated cellular internalization of NPs and offer insights into devising strategies to precisely modulate NP endocytosis by exploiting the interplay between heating and NP properties.

Computational Study on the Regulatory Mechanism of Cell Membrane Wrapping on Liposomes by Embedded Bowl-like Nanostructures for Drug Delivery

Controlling the nanoparticle’s (NP) ability to facilitate cell uptake is particularly desirable for biomedical applications, such as drug delivery. Despite growing evidence highlighting the pivotal role of mechanical properties in biological performances of NPs, consensus regarding how stiffness regulates the cell entry of NPs is lacking. Here, we design and elucidate cell membrane wrapping on soft liposomes in which rigid bowl-like nanostructures are embedded. Compared with pure liposomes, which are often partially wrapped by a membrane due to the high energy barrier associated with the oblate deformation, embedded nanobowls provide physical support to promote wrapping by increasing the liposome rigidity. Through correlating liposome deformation, invagination, and nanobowl orientation, two distinct pathways of cell membrane wrapping on nanobowl-supported liposomes are identified. Different from alternative methods of tuning the rigidity of NPs uniformly, the nanobowl-supported liposome is characterized by mechanical heterogeneity and nanobowl rotation, which correlates with liposome deformation to promote endocytic wrapping. Once the nanobowl’s rotation is restrained, wrapping turns out to be accomplished via membrane protrusion rather than invagination, and the wrapped liposome could be trapped with frustrated internalization and potential membrane perturbation. Following this principle, moderate decreases of the nanobowl size and adhesive strength with the liposome can facilitate the nanobowl’s rotation to promote cell uptake. These results are expected to improve our ability to develop better NPs for enhanced drug delivery.

Role of particle local curvature in cellular wrapping.

Cellular uptake through membranes plays an important role in adsorbing nutrients and fighting infection and can be used for nanomedicine developments. Endocytosis is one of the pathways of cellular uptake which associate with elastic deformation of the membrane wrapping around the foreign particle. The deformability of the membrane is strongly regulated by the presence of a cortical cytoskeleton placed underneath the membrane. It is shown that shape and orientation of the particles influence on their internalization. Here, we study the role of particle local curvature in cellular uptake by investigating the wrapping of an elastic membrane around a long cylindrical object with an elliptical cross-section. The membrane itself is adhered to a substrate mimicking the cytoskeleton. Membrane wrapping proceeds differently whether the initial contact occurs at the target's highly curved part (vertical) or along its long side (horizontal). We obtain a wrapping phase diagram as a function of the membrane-cytoskeleton and the membrane-target adhesion energy, which includes three distinct regimes (unwrapped, partially wrapped and fully wrapped), separated by two phase transitions. We also provide analytical expressions for the boundaries between the different regimes which confirm that the transitions strongly depend on the orientation and aspect ratio of the nanowire.

Human Amniotic Membrane Wrapping of the Ulnar Nerve During Cubital Tunnel Surgery Reduces Recurrence of Symptoms.

Compare the recurrence rate of paresthesias in patients undergoing primary cubital tunnel surgery in those with and without wrapping of the ulnar nerve with the human amniotic membrane (HAM). A retrospective investigation of patients undergoing primary cubital tunnel surgery with a minimum 90-day follow-up was performed. Patients were excluded if the nerve was wrapped using another material, associated traumatic injury, simultaneous Guyon's canal release, or revision procedures. Failure was defined as those patients who experienced initial complete resolution of symptoms (paresthesias) but then developed recurrence of paresthesias. A total of 57 controls (CON) and 21 treated with HAM met our inclusion criteria. There was a difference in the mean age of CON (48.4 ± 13.5 years) and HAM (30.6 ± 15) (P< 0.0001). There was no difference in gender mix (P=0.4), the severity of symptoms (P=0.13), and length of follow-up (P=0.084). None of 21 (0%) treated with HAM developed recurrence of symptoms compared to 11 of 57 (19.3%) (P=0.03) (CON). Using a multivariate regression model adjusted for age and procedure type, CON was 24.4 (95% CI=1.26-500, P=0.0348) times higher risk than HAM of developing a recurrence of symptoms. The HAM wrapping used in primary cubital tunnel surgery significantly reduced recurrence rates of paresthesias. Further prospective studies with randomization should be carried out to better understand the role HAM can play in cubital tunnel surgery.

The Use of Amniotic Membrane for Peripheral Nerve Injury in Lower Extremity Surgical Procedures

Category: Basic Sciences/Biologics; Other Introduction/Purpose: Patients undergoing nerve decompression surgery often report persistent symptoms. Some have suggested that wrapping the affected nerve with amniotic membrane may improve outcomes if the nerve is wrapped with amniotic membrane at the time of surgery, possibly related to anti-inflammatory, antifibrotic, or pro-regenerative effects. There is little in the foot and ankle literature to support such approaches. The aim of this preliminary study was to assess the initial safety of amniotic membrane use outcomes in foot and ankle surgery during nerve decompression procedures as an initial study in anticipation of a randomized, prospective trial. Methods: We retrospectively reviewed outcomes among 22 patients, &gt;=18 years old, who had undergone amniotic membrane neurorrhaphy for lower extremity nerves including sural, saphenous, superficial peroneal, common peroneal, deep peroneal, digital (Morton's neuroma), Baxter's and posterior tibial nerve. Patients may have had multiple nerves wrapped and have had other procedures done. All patients had failed conservative treatments including cortisone injections, orthotics, nonsteroidal anti- inflammatory drugs, and physical therapy. Patients' demographics, postoperative complications, patient reported outcome measures (PROMs), and preoperative/postoperative Visual Analog Scores (VAS) for pain was collected. Data were reported in a descriptive manner. Results: Twenty-two patients, 16 females and 6 males averaging 51 years of age were assessed. Only one patient of the twenty- two reported a higher postoperative VAS compared to the preoperative VAS. There were no post-operative infections or reactions to the amniotic membrane. No patient required repeat surgery. The average pre- and post-operative VAS were 6.36 and 2.77, respectively. The average PROMs Pain Interference and Pain Intensity (Short Form 4a and 3a, respectively) were 42.02 and 35.94, respectively, that were within the normal range. Conclusion: The use of amniotic membrane wrap in lower extremity nerve decompression procedures was shown to be safe regarding post-operative short-term complications in this series of patients. However, in order to prove the usefulness of this technique for pain and function improvement, further studies with larger populations, particularly randomized clinical trials with long term follow up are necessary.

Study on biomimetic nano tumor targeted delivery system for chemotherapy-laser immunotherapy

To explore the immune adjuvant effect of nano mesoporous materials and laser immune effect of cancer therapy combined with chemotherapy, we designed a bionic nano tumor targeting delivery system with homologous cancer cell membrane as the outermost layer. Inorganic mesoporous silica (mSiO2) and hydroxyapatite (HAP) are used as the intermediate immune adjuvant layer and drug carrier layer, and gold nanorods(GNR) are used as the core. It degrade to release drug under the condition of low pH value, and the gold nanorods are wrapped for near-infrared laser response. Homologous cancer cell membrane wrapping is expected to greatly improve the efficiency of targeted delivery. Laser immunotherapy is more widely applied than antibody and vaccine, and has no serious side effects. Combined with controlled release drug targeted chemotherapy and encapsulated with tumor cell membrane, it is expected to further achieve low toxicity and high efficiency cancer treatment.

Selective membrane wrapping on differently sized nanoparticles regulated by clathrin assembly: A computational model

Nanoparticles (NPs) enter cells via multiple pathways, all of which are NP size dependent. Previous studies indicated that the clathrin-mediated endocytosis has different selectivity for the NP size, but the regulatory mechanism remains unclear and difficult to study at the molecular scale in vivo. By means of computer simulation, here we design membrane wrapping on differently sized NPs with mimic clathrin assembly at the opposite membrane side. With relatively large NPs readily wrapped by a pure membrane as manifested, clathrin modulates the process and tunes the size selectivity. Although finite curvature can be generated by cage-like clathrin assembly to facilitate membrane wrapping on relatively small NPs, the clathrin assemblage has a certain range of size, which is mismatched with larger NPs. Besides, the local membrane patch is rigidified by clathrin to increase the barrier of membrane wrapping on larger NPs. Competition of these items determines whether membrane wrapping on NPs is promoted or suppressed, and can be tuned by the NP-membrane adhesion strength, clathrin concentration, and inter-NP distance. Our results highlight the significance of complex environment in altering the nature of NP interaction with cell membranes, and are expected to help design NPs for biomedical applications requiring precise control of NP uptake or cell membrane attachment.

Outcome of human amniotic membrane wrap around neurorrhaphy in high radial nerve injury - a case report following monkey bite

IntroductionPeripheral nerve injury due to animal bite is a rare phenomenon. Most animal bites are from dogs. Monkey bites constitute a common risk, second only to dog bites, among travelers. Peripheral nerve injuries may occur due to a combination of monkey's strong jaws and sharp long teeth penetrating deep into the soft tissues. Such injuries are associated with increased perineural fibrosis. Human amniotic membrane (HAM) wrap around the nerve repair site reduces fibrotic response, prevents adhesions and scar formation thereby improving outcome. We report a case of “High Radial nerve palsy due to monkey bite, treated by neurorrhaphy with HAM wrap”. MethodA 3-year old boy presented with wrist drop, and inability to extend the fingers and thumb of his right dominant hand, following a monkey bite over the distal arm. The diagnosis of high radial nerve injury was corroborated by high frequency ultrasound and electrodiagnostic studies. On exploration the radial nerve was found to be transected. An end to end repair was performed, with HAM wrap around the neurorrhaphy. ResultsWrist dorsiflexion recovered at 2.5 months followed by active finger and thumb extension at 4 months with no infection or immune rejection. ConclusionNerve regeneration in our patient occurred at a faster rate as compared to the conventional 1 mm/day. This could be attributed to decreased perineural fibrosis, improved neurotropism due to the HAM wrap and neuronal plasticity in young brain in addition, the patient being a small child having better regenerative ability in comparison to an adult.

Role of Ligand Distribution in the Cytoskeleton-Associated Endocytosis of Ellipsoidal Nanoparticles

Nanoparticle (NP)–cell interaction mediated by receptor–ligand bonds is a crucial phenomenon in pathology, cellular immunity, and drug delivery systems, and relies strongly on the shape of NPs and the stiffness of the cell. Given this significance, a fundamental question is raised on how the ligand distribution may affect the membrane wrapping of non-spherical NPs under the influence of cytoskeleton deformation. To address this issue, in this work we use a coupled elasticity–diffusion model to systematically investigate the role of ligand distribution in the cytoskeleton-associated endocytosis of ellipsoidal NPs for different NP shapes, sizes, cytoskeleton stiffness, and the initial receptor densities. In this model, we have taken into account the effects of receptor diffusion, receptor–ligand binding, cytoskeleton and membrane deformations, and changes in the configuration entropy of receptors. By solving this model, we find that the uptake process can be significantly influenced by the ligand distribution. Additionally, there exists an optimal state of such a distribution, which corresponds to the fastest uptake efficiency and depends on the NP aspect ratio and cytoskeleton stiffness. We also find that the optimal distribution usually needs local ligand density to be sufficiently high at the large curvature region. Furthermore, the optimal state of NP entry into cells can tolerate slight changes to the corresponding optimal distribution of the ligands. The tolerance to such a change is enhanced as the average receptor density and NP size increase. These results may provide guidelines to control NP–cell interactions and improve the efficiency of target drug delivery systems.

Localized Kaluza-Klein 6-brane

We study the membrane wrapping mode corrections to the Kaluza-Klein (KK) 6-brane in eleven dimensions. We examine the localized KK6-brane in the extended space in E7(7) exceptional field theory. In order to discuss the physical origin of the localization in the extended space, we consider a probe M2-brane in eleven dimensions. We show that a three-dimensional mathcal{N} = 4 gauge theory is naturally interpreted as a membrane generalization of the two-dimensional mathcal{N} = (4, 4) gauged linear sigma model for the fundamental string. We point out that the vector field in the mathcal{N} = 4 model is identified as a dual coordinate of the KK6-brane geometry. We find that the BPS vortex in the gauge theory gives rise to the violation of the isometry along the dual direction. We then show that the vortex corrections are regarded as an instanton effect in M-theory induced by the probe M2-brane wrapping around the M-circle.

Direct visualization of epithelial microvilli biogenesis

Microvilli are actin-bundle-supported surface protrusions that play essential roles in diverse epithelial functions. To develop our understanding of microvilli biogenesis, we used live imaging to directly visualize protrusion growth at early stages of epithelial differentiation. Time-lapse data revealed that specific factors, including epidermal growth factor pathway substrate 8 (EPS8) and insulin-receptor tyrosine kinase substrate (IRTKS) (also known as BAIAP2L1), appear in diffraction-limited puncta at the cell surface and mark future sites of microvillus growth. New core actin bundles elongate from these puncta in parallel with the arrival of ezrin and subsequent plasma membrane encapsulation. In addition to de novo growth, we also observed that new microvilli emerge from pre-existing protrusions. Moreover, we found that nascent microvilli can also collapse, characterized first by loss of membrane wrapping and ezrin enrichment, followed by a sharp decrease in distal tip EPS8 and IRTKS levels, and ultimately disassembly of the core actin bundle itself. These studies are the first to offer a temporally resolved microvillus growth mechanism and highlight factors that participate in this process; they also provide important insights on the growth of apical specializations that will likely apply to diverse epithelial contexts.