Drosophila Mechanical Nociceptors Preferentially Sense Localized Poking

Mechanical nociception is an evolutionarily conserved sensory process required for the survival of living organisms. Previous studies have revealed much about the neural circuits and key sensory molecules in mechanical nociception, but the cellular mechanisms adopted by nociceptors in force detection remain elusive. To address this issue, we study the mechanosensation of a fly larval nociceptor (class IV da neurons, c4da) using a customized mechanical device. We find that c4da are sensitive to mN-scale forces and make uniform responses to the forces applied at different dendritic regions. Moreover, c4da showed a greater sensitivity to more localized forces, consistent with them being able to sense the poking of sharp objects, such as wasp ovipositor. Further analysis reveals that high morphological complexity, mechanosensitivity to lateral tension and active signal propagation in the dendrites altogether facilitate the mechanosensitivity and sensory features of c4da. In particular, we discover that Piezo and Ppk1/Ppk26, two key mechanosensory molecules, make differential but additive contributions to the mechanosensation of c4da. In all, our results provide updates into understanding how c4da process mechanical signals at the cellular level and reveal the contributions of key molecules.

Classic versus High Lateral Tension Abdominoplasty in Post-bariatric Patients

Background: Obesity is a chronic condition with a high prevalence and multifaceted etiologies; it is accompanied by an increased risk of morbidity and mortality. Bariatric surgeries (weight loss surgeries) include a variety of procedures performed on people who have obesity. Skin redundancy is a common post-bariatric complication. Abdominoplasty or "tummy tuck" is a cosmetic surgery procedure used to make the abdomen thinner and more firm. The surgery involves the removal of excess skin and fat from the middle and lower abdomen in order to tighten the muscle and fascia of the abdominal wall. This type of surgery is usually sought by patients with loose or sagging tissues after pregnancy or major weight loss. This study is a comparison between Classic and High lateral tension abdominoplasty techniques in treatment of abdominal skin redundancy in post bariatric patients. In our research, we compared between two techniques of abdominoplasty in treatment of post bariatric abdominal skin redundancy, the classic technique and High Lateral Tension technique, the comparison was in patient satisfaction and in post operative complications The study showed that patient satisfaction was higher in classic technique than the High lateral tension technique due to smaller and less apparent scar, while post operative complications were almost the same in both techniques According to our study, we advise plastic surgeons to perform classic abdominoplasty technique in treatment of post bariatric abdominal skin redundancy.

Mechanosensitive channel gating by delipidation

The mechanosensitive channel of small conductance (MscS) protects bacteria against hypoosmotic shock. It can sense the tension in the surrounding membrane and releases solutes if the pressure in the cell is getting too high. The membrane contacts MscS at sensor paddles, but lipids also leave the membrane and move along grooves between the paddles to reside as far as 15 Å away from the membrane in hydrophobic pockets. One sensing model suggests that a higher tension pulls lipids from the grooves back to the membrane, which triggers gating. However, it is still unclear to what degree this model accounts for sensing and what contribution the direct interaction of the membrane with the channel has. Here, we show that MscS opens when it is sufficiently delipidated by incubation with the detergent dodecyl-β-maltoside or the branched detergent lauryl maltose neopentyl glycol. After addition of detergent-solubilized lipids, it closes again. These results support the model that lipid extrusion causes gating: Lipids are slowly removed from the grooves and pockets by the incubation with detergent, which triggers opening. Addition of lipids in micelles allows lipids to migrate back into the pockets, which closes the channel even in the absence of a membrane. Based on the distribution of the aliphatic chains in the open and closed conformation, we propose that during gating, lipids leave the complex on the cytosolic leaflet at the height of highest lateral tension, while on the periplasmic side, lipids flow into gaps, which open between transmembrane helices.

Increased lateral tension is sufficient for epithelial folding in Drosophila

ABSTRACTThe folding of epithelial sheets is important for tissues, organs and embryos to attain their proper shapes. Epithelial folding requires subcellular modulations of mechanical forces in cells. Fold formation has mainly been attributed to mechanical force generation at apical cell sides, but several studies indicate a role of mechanical tension at lateral cell sides in this process. However, whether lateral tension increase is sufficient to drive epithelial folding remains unclear. Here, we have used optogenetics to locally increase mechanical force generation at apical, lateral or basal sides of epithelial Drosophila wing disc cells, an important model for studying morphogenesis. We show that optogenetic recruitment of RhoGEF2 to apical, lateral or basal cell sides leads to local accumulation of F-actin and increase in mechanical tension. Increased lateral tension, but not increased apical or basal tension, results in sizeable fold formation. Our results stress the diversification of folding mechanisms between different tissues and highlight the importance of lateral tension increase for epithelial folding.

Reversible coating of cells with synthetic polymers for mechanochemical regulation of cell adhesion

The chemical control of cell–cell interactions using synthetic materials is useful for a wide range of biomedical applications. Herein, we report a method to regulate cell adhesion and dispersion by introducing repulsive forces to live cell membranes. To induce repulsion, we tethered amphiphilic polymers, such as cholesterol-modified polyethylene glycol (PEG-CLS) to cell membranes. These amphiphilic polymers both bind to and dissociate rapidly from membranes and thus, enable the reversible coating of cells by mixing and washout without requiring genetic manipulation or chemical synthesis in the cells. We found that the repulsive forces introduced by these tethered polymers can induce cell detachment from a substrate and allow cell dispersion in a suspension, modulate the speed of cell migration, and improve the separation of cells from tissues. Our analyses showed that coating the cells with tethered polymers most likely generated two distinct repulsive forces, lateral tension and steric repulsion, on the surface, which can be tuned by altering the polymer size and density. We also modeled how these two forces can be generated in kinetically distinctive manners to explain the various responses of cells to the coating. Collectively, our observations and analyses show how we can mechanochemically regulate cell adhesion and dispersion and may contribute to the optimization of chemical coating strategies for regulating various types of cell–cell interacting systems.

Nano-wrinkles, compactons, and wrinklons associated with laser-induced Rayleigh–Taylor instability: I. Bubble environment

ABSTRACTWe study dynamics, structure and organization of the new paradigm of wavewrinkle structures associated with multipulse laser-induced RayleighTaylor (RT) instability in the plane of a target surface in the circumferential zone (C-zone) of the spot. Irregular target surface, variation of the fluid layer thickness and of the fluid velocity affect the nonlinearity and dispersion. The fluid layer inhomogeneity establishes local domains arranged (organized) in the «domain network». The traveling wavewrinkles become solitary waves and latter on become transformed into stationary soliton wavewrinkle patterns. Their morphology varies in the radial direction ofaussian-like spot ranging from the compacton-like solitons to the aperiodic rectangular waves (with rounded top surface) and to the periodic ones. These wavewrinkles may be successfully juxtapositioned with the exact solution of the nonlinear differential equations formulated in the KadomtsevPetviashvili sense taking into account the fluid conditions in particular domain. The cooling wave that starts at the periphery by the end of the pulse causes sudden increase of density and surface tension: the wavewrinkle structures become unstable what causes their break-up. The onset of solidification causes formation of an elastic sheet which starts to shrink generating lateral tension on the wavewrinkles. The focusing of energy at the constrained boundary causes the formation of wrinklons as the new elementary excitation of the elastic sheets.

Amphipathic molecules modulate PIEZO1 activity

PIEZO proteins are large eukaryotic mechanically-gated channels that function as homotrimers. The basic PIEZO1 structure has been elucidated by CryoEM and it assembles into a protein–lipid dome. A curved lipid region allows for the transition to the lipid bilayer from the dome (footprint). Gating PIEZO1 is mediated by bilayer tension that induces an area change in the lipid dome. The footprint region is thought to be energetically important for changes in lateral tension. Amphipathic molecules can modulate channel function beyond the intrinsic gating properties of PIEZO1. As a result, molecules that modify lipid properties within the lipid–channel complex (footprint and dome) will profoundly affect channel kinetics. In this review, we summarize the effects some amphipathic molecules have on the lipid bilayer and PIEZO1 function. PIEZO1 has three states, closed, open and inactivated and amphipathic molecules influence these transitions. The amphipathic peptide, GsMTx4, inhibits the closed to open transition. While saturated fatty acids also prevent PIEZO1 gating, the effect is mediated by stiffening the lipids, presumably in both the dome and footprint region. Polyunsaturated fatty acids can increase disorder within the lipid–protein complex affecting channel kinetics. PIEZO1 can also form higher-ordered structures that confers new kinetic properties associated with clustered channels. Cholesterol-rich domains house PIEZO1 channels, and depletion of cholesterol causes a breakdown of those domains with changes to channel kinetics and channel diffusion. These examples underscore the complex effects lipophilic molecules can have on the PIEZO1 lipid dome structure and thus on the mechanical response of the cell.

PO 18236 - Assessment of hallux valgus reduction using a modified version of the McBride test

Introduction: The McBride test was created to assess hallux valgus reduction and is also used to assess capsular and lateral soft-tissue tension indicating the need for lateral capsular release after the bone procedure in the first metatarsal bone. The flowcharts for lateral soft-tissue release remain unclear and lack consensus among surgeons. Objective: To propose a modified version of the test for the complementary preoperative assessment of hallux valgus reduction. Methods: We describe a method in which the examiner supinates the first metatarsal head medially to manually correct the pronation of the first metatarsal and then applies varus force to the hallux to test the lateral capsular tension of the metatarsophalangeal joint. Results: A significant reduction in lateral capsular tension was observed in the metatarsal head lifting and rotating maneuver compared with the conventional McBride test. Discussion: Hallux valgus reduction is greater with manual correction of the deformity than with the classic McBride test, most likely because of the resulting rotational bone repositioning and soft-tissue balancing. These changes seem to decrease the lateral tension that limits the correction of the deformity in the metatarsophalangeal angular plane. Conclusion: We believe that this modified version of the McBride test can be used as a more reliable predictor of the need for lateral metatarsophalangeal release after the metatarsal position is corrected through osteotomy or cuneometatarsal arthrodesis.