Caveolae promote successful abscission by controlling intercellular bridge tension during cytokinesis

During cytokinesis, the intercellular bridge (ICB) connecting the daughter cells experiences pulling forces, which delay abscission by preventing the assembly of the ESCRT scission machinery. Abscission is thus triggered by tension release, but how ICB tension is controlled is unknown. Here, we report that caveolae, which are known to control membrane tension upon mechanical stress in interphase cells, are located at the midbody, at the abscission site and at the ICB/cell interface in dividing cells. Functionally, the loss of caveolae delays ESCRT-III recruitment during cytokinesis and impairs abscission. This is the consequence of a 2-fold increase of ICB tension measured by laser ablation, associated with a local increase in myosin II activity at the ICB/cell interface. We thus propose that caveolae buffer membrane tension and limit contractibility at the ICB to promote ESCRT-III assembly and cytokinetic abscission. Altogether, this work reveals an unexpected connection between caveolae and the ESCRT machinery and the first role of caveolae in cell division.

Optical Pulling Using Chiral Metalens as a Photonic Probe

Optical pulling forces, which can pull objects in the source direction, have emerged as an intensively explored field in recent years. Conventionally, optical pulling forces exerted on objects can be achieved by tailoring the properties of an electromagnetic field, the surrounding environment, or the particles themselves. Recently, the idea of applying conventional lenses or prisms as photonic probes has been proposed to realize an optical pulling force. However, their sizes are far beyond the scope of optical manipulation. Here, we design a chiral metalens as the photonic probe to generate a robust optical pulling force. The induced pulling force exerted on the metalens, characterized by a broadband spectrum over 0.6 μm (from 1.517 to 2.117 μm) bandwidth, reached a maximum value of −83.76 pN/W. Moreover, under the illumination of incident light with different circular polarization states, the longitudinal optical force acting on the metalens showed a circular dichroism response. This means that the longitudinal optical force can be flexibly tuned from a pulling force to a pushing force by controlling the polarization of the incident light. This work could pave the way for a new advanced optical manipulation technique, with potential applications ranging from contactless wafer-scale fabrication to cell assembly and even course control for spacecraft.

Design and Simulation of Fiber Optic Cable using SolidWorks for Landslide Monitoring

This paper presents fiber optic cable design and simulation using SolidWorks software. SolidWorks software is an effective tool that helps design, analyze, and give a better understanding of fiber optic cable capabilities and performances. The model of the fiber optic cable was developed based on the existing fiber optic drop cable. It is composed of mainly four parts: Fiber optic member, fiber-reinforced plastic (FRP) strength member, low smoke zero halogen (LSZH) jacket, and steel wire. A static study was performed to determine the designed model’s ability to endure various levels of pressing and pulling forces. Simulation results showed that the cable can withstand a maximum of 195 N pulling force and 30000 N pressing force with a displacement of 1.78e+02 mm and 4.94e-01 mm respectively. The findings will contribute to the design of a new or novel fiber optic cable that is capable to monitor landslide activities with higher durability in future studies.

Laser Ablation and Fluid Flows Show a Single Force Mechanism Governs Spindle Positioning

Few techniques are available for elucidating the nature of forces that drive subcellular behaviors. Here we develop two complementary ones: 1) femtosecond stereotactic laser ablation (FESLA), which rapidly creates complex cuts of subcellular structures, thereby allowing precise dissection of when, where, and in what direction forces are generated; and 2) assessment of subcellular fluid flows, by comparing direct flow measurements, using microinjected fluorescent nanodiamonds, to large-scale fluid-structure simulations of different models of force transduction. We apply these to study centrosomes in Caenorhabditis elegans early embryos, and use the data to construct a biophysically-based model of centrosome dynamics. Taken together, we demonstrate that cortical pulling forces provide a general explanation for many behaviors mediated by centrosomes, including pronuclear migration/centration and rotation, metaphase spindle positioning, asymmetric spindle elongation and spindle oscillations. In sum, this work establishes new methodologies for disentangling the forces responsible for cell biological phenomena.

Cortical microtubule pulling forces contribute to the union of the parental genomes in the C. elegans zygote

Previously, we reported that the Polo-like kinase PLK-1 phosphorylates the single C. elegans lamin (LMN-1) to trigger lamina depolymerization during mitosis. We showed that this event is required for the formation of a pronuclear envelopes scission event that removes membranes on the juxtaposed oocyte and sperm pronuclear envelopes in the zygote, allowing the parental chromosomes to merge in a single nucleus after segregation (Velez-Aguilera, 2020). Here we show that cortical microtubule pulling forces contribute to pronuclear envelopes scission by promoting mitotic spindle elongation. We also demonstrate that weakening of the pronuclear envelopes, via PLK-1-mediated lamina depolymerization, is a prerequisite for the astral microtubule pulling forces to trigger pronuclear membranes scission. Finally, we provide evidence that PLK-1 mainly acts via lamina depolymerization in this process. These observations thus indicate that temporal coordination between lamina depolymerization and mitotic spindle elongation facilitates pronuclear envelopes scission and parental genomes unification.

Mechanics of cell integration in vivo

During embryonic development, regeneration and homeostasis, cells have to physically integrate into their target tissues, where they ultimately execute their function. Despite a significant body of research on how mechanical forces instruct cellular behaviors within the plane of an epithelium, very little is known about the mechanical interplay at the interface between migrating cells and their surrounding tissue, which has its own dynamics, architecture and identity. Here, using quantitative in vivo imaging and molecular perturbations, together with a theoretical model, we reveal that multiciliated cell (MCC) precursors in the Xenopus embryo form dynamic filopodia that pull at the vertices of the overlying epithelial sheet to probe their stiffness and identify the preferred positions for their integration into the tissue. Moreover, we report a novel function for a structural component of vertices, the lipolysis-stimulated lipoprotein receptor (LSR), in filopodia dynamics and show its critical role in cell intercalation. Remarkably, we find that pulling forces equip the MCCs to remodel the epithelial junctions of the neighboring tissue, enabling them to generate a permissive environment for their integration. Our findings reveal the intricate physical crosstalk at the cell-tissue interface and uncover previously unknown functions for mechanical forces in orchestrating cell integration.

P048 A NEW MODALITY FOR BIOMECHANICAL VALIDATION OF CLOSURE TECHNIQUES OF LAPAROTOMIES

Aim Incisional hernia remains one of the most frequent complications after abdominal surgery. Several closure techniques exist. However, fundamental biomechanical understanding of these techniques and of the differences in clinical outcomes are still lacking. It is thought that distribution of lateral forces on the midline plays a role. Testing in a clinical setting is limited by sample sizes, costs and ethical regulations. We propose a preclinical ex vivo model in which multiple closure configurations can be tested in a controlled setting, eliminating interfering variables existing in previously published, more complex abdominal wall models. Consequently, this allows a valid comparison between closure modalities based on biomechanical merits. Material and Methods The experimental set-up is represented by a vertical tensile load tester, in which a sutured tissue sample is clamped. The tissue samples are covered with a fine, random speckle pattern via miniscule ink droplets. A high-resolution camera captures the speckles as the tissue is subjected to linear pulling forces. Image analysis documenting relative movement of speckles as a means for measuring tissue deformation is performed in ex-vivo tissue samples, resulting in specific objective biomechanical characteristics for each closure configuration. Results Local tissue strain fields are visualized, and compared between closure modalities and correlated to known linear forces applied to the tissue. The latest results will be shared and discussed. Conclusions A new modality for biomechanical evaluation of closure techniques has been developed. Further validation and serial experiments with different closure modalities with and without mesh reinforcement can be performed in order to determine the biomechanically optimal suture-technique for fascial closure.

Mechanically active integrins direct cytotoxic secretion at the immune synapse

The secretory output of cell-cell interfaces must be tightly controlled in space and time to ensure functional efficacy. This is particularly true for the cytotoxic immune synapse (IS), the stereotyped junction formed between a cytotoxic lymphocyte and the infected or transformed target cell it aims to destroy. Cytotoxic lymphocytes kill their targets by channeling a mixture of granzyme proteases and the pore forming protein perforin directly into the IS. The synaptic secretion of these toxic molecules constrains their deleterious effects to the target cell alone, thereby protecting innocent bystander cells in the surrounding tissue from collateral damage. Despite the importance of this process for immune specificity, the molecular and cellular mechanisms that establish secretory sites within the IS remain poorly understood. Here, we identified an essential role for integrin mechanotransduction in cytotoxic secretion using a combination of single cell biophysical measurements, ligand micropatterning, and functional assays. Upon ligand-binding, the αLβ2 integrin LFA-1 functioned as a spatial cue, attracting lytic granules containing perforin and granzyme and inducing their fusion at closely adjacent sites within the synaptic membrane. LFA-1 molecules were subjected to pulling forces within these secretory domains, and genetic or pharmacological suppression of these forces abrogated cytotoxicity. We conclude that lymphocytes employ an integrin-dependent mechanical checkpoint to enhance both the potency and the security of their cytotoxic output.

Analysis of Tug of War Competition. A Narrative Complete Review

Tug-of-war (TOW) is an internationally played activity including professional and amateur athletes and defined as early (4000 years ago as a rope less version) in the artwork on Egyptian tomb engravings and is played as per the rules laid out by TWIF, which has 73 member countries and administrative headquarters in the USA. Typically, two teams of “pullers” participate and apply enormous contra directional forces on the pulling rope. Originally, two types of competition are used: knockout and points. This narrative review describes the scientific state of the art about of TOW. For the best of the author’s knowledge no previous information has been published. Anthropometric parameters are near 83.6, lean body mass 69.4, and body fat 16. The VO2MAX is 55.8 ml/kg/min. Relative strength, the dynamic leg power was 4659.8 N. Endurance TOW elicits minimal muscle damage. The injured strains and sprains comprised over half of all injuries: back (42%), shoulder–upper limb (23%) and knee (17%). Pulling movement in TOW contests can be divided into three phases: namely "Drop", "Hold" and "Drive" phase. The maximal pulling forces was 1041.6 ± 123.9 N. The percentage of dynamic pulling force in static maximal pulling force was 75.5 ± 14.4% and the dynamic ranged from 106.4 to 182.5%. There are two gripping styles, indoor and outdoor. The friction characteristics between surface and shoe in TOW is important to determine a suitable shoe for indoor TOW. Waist Belt might be a useful piece of equipment for TOW sport. The EMG technique in Tow described a high activity of dorsal muscle during the pulling. The factor of force vanishing was the coordination among athletes. The force vanishing percentage goes from 8.82±5.59 for 2 contenders to 19.74±2.22 for 8 athletes, 6.4 % in the sum of 2 pullers. However, in the drop phase, for female elite TOW team, only the 0.5 % of them pulling force was wasted. Future studies are need in order to understand better this historical sport activity.