Red blood cell flickering activity locally controlled by holographic optical tweezers.

Red blood cells possess a singular mechanobiology, enabling efficient navigation through capillaries smaller than their own size. Their plasma membrane exhibits non-equilibrium shape fluctuation, often reported as enhanced flickering activity. Such active membrane motion is propelled by motor proteins that mediate interactions between the spectrin skeleton and the lipid bilayer.

Mechanical stress confers nuclear and functional changes in derived leukemia cells from persistent confined migration.

Nuclear deformability plays a critical role in cell migration. During this process, the remodeling of internal components of the nucleus has a direct impact on DNA damage and cell behavior; however, how persistent migration promotes nuclear changes leading to phenotypical and functional consequences remains poorly understood. Here, we described that the persistent migration through physical barriers was sufficient to promote permanent modifications in migratory-altered cells.

Inhomogeneous Canham-Helfrich Abscission in Catenoid Necks under Critical Membrane Mosaicity.

The mechanical effects of membrane compositional inhomogeneities are analyzed in a process analogous to neck formation in cellular membranes. We cast on the Canham-Helfrich model of fluid membranes with both the spontaneous curvature and the surface tension being non-homogeneous functions along the cell membrane. The inhomogeneous distribution of necking forces is determined by the equilibrium mechanical equations and the boundary conditions as considered in the axisymmetric setting compatible with the necking process.

Rheology of Pseudomonas fluorescens biofilms: From experiments to predictive DPD mesoscopic modeling.

Bacterial biofilms mechanically behave as viscoelastic media consisting of micron-sized bacteria cross-linked to a self-produced network of extracellular polymeric substances (EPSs) embedded in water. Structural principles for numerical modeling aim at describing mesoscopic viscoelasticity without losing details on the underlying interactions existing in wide regimes of deformation under hydrodynamic stress. Here, we approach the computational challenge to model bacterial biofilms for predictive mechanics in silico under variable stress conditions.

Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation.

Inhibition of the heterodimeric amino acid carrier SLC7A5/SLC3A2 (LAT1/CD98) has been widely studied in tumor biology but its role in physiological conditions remains largely unknown. Here we show that the SLC7A5/SLC3A2 heterodimer is constitutively present at different stages of erythroid differentiation but absent in mature erythrocytes. Administration of erythropoietin (EPO) further induces SLC7A5/SLC3A2 expression in circulating reticulocytes, as it also occurs in anemic conditions.

Lipid nanoparticles for antisense oligonucleotide gene interference into brain border-associated macrophages.

A colloidal synthesis' proof-of-concept based on the Bligh-Dyer emulsion inversion method was designed for integrating into lipid nanoparticles (LNPs) cell-permeating DNA antisense oligonucleotides (ASOs), also known as GapmeRs (GRs), for mRNA interference. The GR@LNPs were formulated to target brain border-associated macrophages (BAMs) as a central nervous system (CNS) therapy platform for silencing neuroinflammation-related genes. We specifically aim at inhibiting the expression of the gene encoding for lipocalin-type prostaglandin D synthase (L-PGDS), an anti-inflammatory enzyme expressed in BAMs, whose level of expression is altered in neuropsychopathologies such as depression and schizophrenia.

Membrane rigidity regulates E. coli proliferation rates.

Combining single cell experiments, population dynamics and theoretical methods of membrane mechanics, we put forward that the rate of cell proliferation in E. coli colonies can be regulated by modifiers of the mechanical properties of the bacterial membrane. Bacterial proliferation was modelled as mediated by cell division through a membrane constriction divisome based on FtsZ, a mechanically competent protein at elastic interaction against membrane rigidity.

Moulding hydrodynamic 2D-crystals upon parametric Faraday waves in shear-functionalized water surfaces.

Faraday waves, or surface waves oscillating at half of the natural frequency when a liquid is vertically vibrated, are archetypes of ordering transitions on liquid surfaces. Although unbounded Faraday waves patterns sustained upon bulk frictional stresses have been reported in highly viscous fluids, the role of surface rigidity has not been investigated so far. Here, we demonstrate that dynamically frozen Faraday waves-that we call 2D-hydrodynamic crystals-do appear as ordered patterns of nonlinear gravity-capillary modes in water surfaces functionalized with soluble (bio)surfactants endowing in-plane shear stiffness.

Multiple particle tracking analysis in isolated nuclei reveals the mechanical phenotype of leukemia cells.

The nucleus is fundamentally composed by lamina and nuclear membranes that enclose the chromatin, nucleoskeletal components and suspending nucleoplasm. The functional connections of this network integrate external stimuli into cell signals, including physical forces to mechanical responses of the nucleus. Canonically, the morphological characteristics of the nucleus, as shape and size, have served for pathologists to stratify and diagnose cancer patients; however, novel biophysical techniques must exploit physical parameters to improve cancer diagnosis.

Mechanical conditions for stable symmetric cell constriction.

Cell constriction is a decisive step for division in many cells. However, its physical pathway remains poorly understood, calling for a quantitative analysis of the forces required in different cytokinetic scenarios. Using a model cell composed by a flexible membrane (actin cortex and cell membrane) that encloses the cytoplasm, we study the mechanical conditions necessary for stable symmetric constriction under radial equatorial forces using analytical and numerical methods.

Membrane curvature induces cardiolipin sorting.

Cardiolipin is a cone-shaped lipid predominantly localized in curved membrane sites of bacteria and in the mitochondrial cristae. This specific localization has been argued to be geometry-driven, since the CL's conical shape relaxes curvature frustration. Although previous evidence suggests a coupling between CL concentration and membrane shape in vivo, no precise experimental data are available for curvature-based CL sorting in vitro.

Microfluidic fabrication of vesicles with hybrid lipid/nanoparticle bilayer membranes.

Hybrid lipid/nanoparticle membranes are suitable model systems both to study the complex interactions between nanoparticles and biological membranes, and to demonstrate technological concepts in cellular sensing and drug delivery. Unfortunately, embedding nanoparticles into the bilayer membrane of lipid vesicles is challenging due to the poor control over the vesicle fabrication process of conventional methodologies and the fragility of the modified lipid bilayer assembly. Here, the utility of water-in-oil-in-water double emulsion drops with ultrathin oil shells as templates to form vesicles with hybrid lipid/nanoparticle membranes is reported.

A gradient-based, GPU-accelerated, high-precision contour-segmentation algorithm with application to cell membrane fluctuation spectroscopy.

We present a novel intensity-gradient based algorithm specifically designed for nanometer-segmentation of cell membrane contours obtained with high-resolution optical microscopy combined with high-velocity digital imaging. The algorithm relies on the image oversampling performance and computational power of graphical processing units (GPUs). Both, synthetic and experimental data are used to quantify the sub-pixel precision of the algorithm, whose analytic performance results comparatively higher than in previous methods.

Injectable Hybrid Hydrogels, with Cell-Responsive Degradation, for Tumor Resection.

Biocompatible soft materials have recently found applications in interventional endoscopy to facilitate resection of mucosal tumors. When neoplastic lesions are in organs that can be easily damaged by perforation, such as stomach, intestine, and esophagus, the formation of a submucosal fluid cushion (SFC) is needed to lift the tumor from the underlying muscle during the resection of neoplasias. Such procedure is called endoscopic submucosal dissection (ESD).

Supramolecular zippers elicit interbilayer adhesion of membranes producing cell death.

Background: The fluorescent dye 10-N-nonyl acridine orange (NAO) is widely used as a mitochondrial marker. NAO was reported to have cytotoxic effects in cultured eukaryotic cells when incubated at high concentrations. Although the biochemical response of NAO-induced toxicity has been well identified, the underlying molecular mechanism has not yet been explored in detail.

WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment.

Cell migration through extracellular matrices requires nuclear deformation, which depends on nuclear stiffness. In turn, chromatin structure contributes to nuclear stiffness, but the mechanosensing pathways regulating chromatin during cell migration remain unclear. Here, we demonstrate that WD repeat domain 5 (WDR5), an essential component of H3K4 methyltransferase complexes, regulates cell polarity, nuclear deformability, and migration of lymphocytes in vitro and in vivo, independent of transcriptional activity, suggesting nongenomic functions for WDR5.

Nonequilibrium fluctuations of lipid membranes by the rotating motor protein FF-ATP synthase.

ATP synthase is a rotating membrane protein that synthesizes ATP through proton-pumping activity across the membrane. To unveil the mechanical impact of this molecular active pump on the bending properties of its lipid environment, we have functionally reconstituted the ATP synthase in giant unilamellar vesicles and tracked the membrane fluctuations by means of flickering spectroscopy. We find that ATP synthase rotates at a frequency of about 20 Hz, promoting large nonequilibrium deformations at discrete hot spots in lipid vesicles and thus inducing an overall membrane softening.

Aescin Incorporation and Nanodomain Formation in DMPC Model Membranes.

The saponin aescin from the horse chestnut tree is a natural surfactant well-known to self-assemble as oriented-aggregates at fluid interfaces. Using model membranes in the form of lipid vesicles and Langmuir monolayers, we study the mixing properties of aescin with the phase-segregating phospholipid 1,2-dimyristoyl-sn-glycero-phosphocholine (DMPC). The binary membranes are experimentally studied on different length scales ranging from the lipid headgroup area to the macroscopic scale using small-angle X-ray scattering (SAXS), photon correlation spectroscopy (PCS), and differential scanning calorimetry (DSC) with binary bilayer vesicles and Langmuir tensiometry (LT) with lipid monolayers spread on the surface of aescin solutions.

Dissipative dynamics of fluid lipid membranes enriched in cholesterol.

Cholesterol is an intriguing component of fluid lipid membranes: It makes them stiffer but also more fluid. Despite the enormous biological significance of this complex dynamical behavior, which blends aspects of membrane elasticity with viscous friction, their mechanical bases remain however poorly understood. Here, we show that the incorporation of physiologically relevant contents of cholesterol in model fluid membranes produces a fourfold increase in the membrane bending modulus.

The enzymatic sphingomyelin to ceramide conversion increases the shear membrane viscosity at the air-water interface.

Whereas most of lipids have viscous properties and they do not have significant elastic features, ceramides behave as very rigid solid assemblies, displaying viscoelastic behaviour at physiological temperatures. The present review addresses the surface rheology of lipid binary mixtures made of sphingomyelin and ceramide. However, ceramide is formed by the enzymatic cleavage of sphingomyelin in cell plasma membranes.

Surface hydrodynamics of viscoelastic fluids and soft solids: Surfing bulk rheology on capillary and Rayleigh waves.

From the recent advent of the new soft-micro technologies, the hydrodynamic theory of surface modes propagating on viscoelastic bodies has reinvigorated this field of technology with interesting predictions and new possible applications, so recovering its scientific interest very limited at birth to the academic scope. Today, a myriad of soft small objects, deformable meso- and micro-structures, and macroscopically viscoelastic bodies fabricated from colloids and polymers are already available in the materials catalogue. Thus, one can envisage a constellation of new soft objects fabricated by-design with a functional dynamics based on the mechanical interplay of the viscoelastic material with the medium through their interfaces.

Modeling the Mechanics of Cell Division: Influence of Spontaneous Membrane Curvature, Surface Tension, and Osmotic Pressure.

Many cell division processes have been conserved throughout evolution and are being revealed by studies on model organisms such as bacteria, yeasts, and protozoa. Cellular membrane constriction is one of these processes, observed almost universally during cell division. It happens similarly in all organisms through a mechanical pathway synchronized with the sequence of cytokinetic events in the cell interior.

Nanomechanical properties of composite protein networks of erythroid membranes at lipid surfaces.

Erythrocyte membranes have been particularly useful as a model for studies of membrane structure and mechanics. Native erythroid membranes can be electroformed as giant unilamellar vesicles (eGUVs). In the presence of ATP, the erythroid membrane proteins of eGUVs rearrange into protein networks at the microscale.