Mechanical Interaction Research Articles

Polarity-driven three-dimensional spontaneous rotation of a cell doublet

Mechanical interactions between cells play a fundamental role in the self-organization of organisms. How these interactions drive coordinated cell movement in three dimensions remains unclear. Here we report that cell doublets embedded in a three-dimensional extracellular matrix undergo spontaneous rotations. We investigate the rotation mechanism and find that it is driven by a polarized distribution of myosin within cell cortices. The mismatched orientation of this polarized distribution breaks the doublet mirror symmetry. In addition, cells adhere at their interface through adherens junctions and with the extracellular matrix through focal contacts near myosin clusters. We use a physical theory describing the doublet as two interacting active surfaces to show that rotation is driven by myosin-generated gradients of active tension whose profiles are dictated by interacting cell polarity axes. We also show that three-dimensional shape symmetries are related to broken symmetries of the myosin distribution in cortices. To test for the rotation mechanism, we suppress myosin clusters using laser ablation and generate new myosin clusters by optogenetics. Our work clarifies how polarity-oriented active mechanical forces drive collective cell motion in three dimensions.

Notch corrosion fatigue behaviour and simplified strain energy density-based notch fatigue life assessment of Grade-A shipbuilding steel

Corrosion fatigue is a key challenge in lifecycle management of ship hull structures. Although sea wave fatigue stresses are linear-elastic, highly-damaging elastic–plastic conditions occur at geometrical discontinuities or notches. Estimation of notch stress-strains to characterize notch fatigue behaviour conventionally requires large computational efforts. Also, constant strain energy density (SED), as a driving force, is far more effective in realistic applications versus constant stress and strain fatigue life approaches. Identified research gaps were the development of a simplified SED approach for fatigue life assessment of hole-notched structures. Fatigue studies were conducted on hole-notched specimens of Grade-A shipbuilding steel in air and corrosion mediums. Strong synergistic interactions of corrosion and fatigue damage mechanisms were studied by scanning electron microscope (SEM) fractography. Notch corrosion fatigue life was reduced by 70% from notch air fatigue life due to environmental effect. Two new parameters are proposed to improve the efficiency of notch fatigue life assessment, namely “fatigue notch strain energy density concentration factor (K_SED) and “fatigue notch toughness”. This improved fatigue life assessment method was demonstrated as equally reliable but much simpler to implement, eliminating the complex computational analysis. This improved method has promising applications in real-time structural health monitoring (SHM) of ship hull structures.

Interfacial debonding in a thin plate bonded to a rigid substrate with a circular hole

Mode I fracture is a prevalent failure mode in adhesively bonded joints. This paper presents analytical and numerical solutions for the mechanical interaction of a thin plate bonded to a rigid substrate with a circular hole. Utilizing the bilinear cohesive law, the proposed solution is designed for the bonded joints subjected to uniformly distributed load and point load, respectively. The interfacial normal stress distribution and load-displacement response undergo three distinct stages: the initial elastic stage, followed by the elastic-softening stage, and culminating in the elastic-softening-debonding stage. The load-displacement response of the joints subjected to uniformly distributed load and point load diverges after debonding occurs. The load-carrying capacity of the former decreases rapidly, while the latter exhibits an opposite trend. Finite element (FE) simulation is conducted for numerical validation, demonstrating excellent agreement between the proposed model and FE results. The paper concludes by discussing the influences of hole radius, bond length, and the properties of the adhesive layer and thin plate on load-displacement response and the ultimate load. The findings suggest that higher bond strength and larger fracture energy of the adhesive, along with thicker and stiffer thin plates, contribute to achieving higher load-carrying capacity in bonded joints. Additionally, a longer bond length improves the load-carrying capacity for the joint subjected to the point load, with minimal impact for uniformly distributed loads once the bond length exceeds the effective bond length.

Investigating the Influence of Varied Particle Sizes on the Load-Bearing Properties of Arrester Bed Aggregates.

This study employs the discrete element method to investigate the influence of particle size on the load-bearing characteristics of aggregates, with a specific emphasis on the aggregates used in escape ramp arrester beds. This study utilises the log edge detection algorithm to introduce an innovative approach for modelling irregularly shaped pebbles, integrating their physical properties into a comprehensive discrete element model to enhance the accuracy and applicability of simulations involving such pebbles. Meticulous validation and parameter calibration (friction coefficient: 0.37, maximum RMSE: 3.43) confirm the accuracy of the simulations and facilitate an in-depth examination of the mechanical interactions between aggregate particles at macroscopic and microscopic scales. The findings reveal a significant relationship between the particle size and load-bearing capacity of aggregates. Smaller pebbles, which are more flexible under pressure, can be packed more densely, thereby improving the distribution of vertical forces and increasing the concentration of local stress. This enhancement substantially increases the overall load-bearing capacity of aggregates. These discoveries hold significant implications for engineering practices, particularly in the optimisation of safety for truck escape ramps and in identifying the ideal sizes of pebbles with irregular shapes.

Mechanics limits ecological diversity and promotes heterogeneity in confined bacterial communities

Multispecies bacterial populations often inhabit confined and densely packed environments where spatial competition determines the ecological diversity of the community. However, the role of mechanical interactions in shaping the ecology is still poorly understood. Here, we study a model system consisting of two populations of nonmotile Escherichia coli bacteria competing within open, monolayer microchannels. The competitive dynamics is observed to be biphasic: After seeding, either one strain rapidly fixates or both strains orient into spatially stratified, stable communities. We find that mechanical interactions with other cells and local spatial constraints influence the resulting community ecology in unexpected ways, severely limiting the overall diversity of the communities while simultaneously allowing for the establishment of stable, heterogeneous populations of bacteria displaying disparate growth rates. Surprisingly, the populations have a high probability of coexisting even when one strain has a significant growth advantage. A more coccus morphology is shown to provide a selective advantage, but agent-based simulations indicate this is due to hydrodynamic and adhesion effects within the microchannel and not from breaking of the nematic ordering. Our observations are qualitatively reproduced by a simple Pólya urn model, which suggests the generality of our findings for confined population dynamics and highlights the importance of early colonization conditions on the resulting diversity and ecology of bacterial communities. These results provide fundamental insights into the determinants of community diversity in dense confined ecosystems where spatial exclusion is central to competition as in organized biofilms or intestinal crypts.

An integrated assessment of erosion drivers facilitating gully expansion rates—A near century multi‐temporal analysis from South Africa

AbstractRural areas in the Eastern Cape Province of South Africa are severely affected by gully erosion, yet little is known about the rates at which these features are expanding. This study explores the areal extent, physical mechanisms, rates, and drivers of gully expansion with the aim of investigating how erosion rates fluctuate in response to temporal variations of drivers over the last century. Investigations involved the creation of an erosion inventory geo‐database, the identification of area‐specific physical expansion mechanisms, an assessment of static and dynamic drivers, and a multi‐temporal study of 25 gullies in the Mthatha area. Results show gully erosion affects 2.3% of the study area, with gullies exhibiting an average annual areal increase of 2.08%, a sidewall retreat rate of 0.2 m/y, and a headcut retreat of 1.03 m/y over an 82‐year period between 1938 and 2020. A multi‐temporal case study of the Ngwevana Gully showed average annual areal growth rates ranging from 3.9% between 1938 and 1948 to 0.7% between 2017 and 2020. Findings indicate that although gullies consistently expand their areal footprint, they do so at fluctuating rates. An assessment of erosion drivers reveals that temporal promotion or suppression of these erosion rates occurs in response to the complex and dynamic interactions of both natural mechanisms and anthropogenic activities. In Mthatha, the periods of increased rates of erosion are linked to large‐scale flooding events during drier climate cycles, which were further exacerbated by invasive dryland agricultural practices, inappropriate land use, haphazard infrastructure development, and rapid population increases facilitated by past Apartheid settlement laws.

Mechanical and piezoresistive performance of additively manufactured carbon fiber/PA12 hybrid honeycombs

This study investigates a novel self-sensing honeycomb composite structure composed of two distinct cellular layers with differing unit cell architectures, specifically hexagonal and re-entrant designs. Short carbon fiber (CF)/polyamide 12 (PA12) composite filaments with 0, 5 or 15 wt.% CF content were utilized to additively manufacture the honeycomb structures via Fused Filament Fabrication (FFF), and their mechanical and piezoresistive self-sensing characteristics were experimentally investigated under quasi-static in-plane and out-of-plane compression at both room temperature and elevated temperatures. The results reveal that the hybrid hexagonal/re-entrant (HR) honeycombs mechanically outperform their non-hybrid double-layer and single-layer counterparts under in-plane loading, reporting an increase in collapse strength and energy absorption by factors of 1.64 and 2.25, respectively. These improvements are attributed to the mechanical interactions occurring at the interface between the auxetic and non-auxetic layers within the hybrid structure, effectively enhancing its structural attributes. Furthermore, the double-layer honeycombs display excellent strain-sensing capabilities within the elastic regime, with gauge factors reaching values as high as 146. Mechanical tests conducted at elevated temperatures reveal that the CF/PA12 honeycombs retain a significant portion of their elastic modulus, strength and energy absorption even at 125 °C, while maintaining high gauge factors of up to 72.4. These honeycombs also exhibit pronounced thermoresistive behavior, evidenced by a decrease in electrical resistance of up to 41.3 % with increasing temperatures from 25 to 125 °C. Considering their exceptional combination of thermo-mechanical, thermoresistive and piezoresistive characteristics, these hybrid double-layered CF/PA12 honeycombs hold promise for potential applications in multifunctional lightweight structures, offering integrated temperature and strain-sensing capabilities.

Synergistic Effects of Matrix Biophysical Properties on Gastric Cancer Cell Behavior via Integrin-Mediated Cell-ECM Interactions.

The biophysical properties of the extracellular matrix (ECM) play a pivotal role in modulating cancer progression via cell-ECM interactions. However, the biophysical properties specific to gastric cancer (GC) remain largely unexplored. Pertinently, GC ECM shows significantly heterogeneous metamorphoses, such as matrix stiffening and intricate restructuring. By combining collagen I and alginate, this study designs an in vitro biomimetic hydrogel platform to independently modulate matrix stiffness and structure across a physiological stiffness spectrum while preserving consistent collagen concentration and fiber topography. With this platform, this study assesses the impacts of matrix biophysical properties on cell proliferation, migration, invasion, and other pivotal dynamics of AGS. The findings spotlight a compelling interplay between matrix stiffness and structure, influencing both cellular responses and ECM remodeling. Furthermore, this investigation into the integrin/actin-collagen interplay reinforces the central role of integrins in mediating cell-ECM interactions, reciprocally sculpting cell conduct, and ECM adaptation. Collectively, this study reveals a previously unidentified role of ECM biophysical properties in GC malignant potential and provides insight into the bidirectional mechanical cell-ECM interactions, which may facilitate the development of novel therapeutic horizons.

Reverse engineering morphogenesis through Bayesian optimization of physics-based models

Morphogenetic programs coordinate cell signaling and mechanical interactions to shape organs. In systems and synthetic biology, a key challenge is determining optimal cellular interactions for predicting organ shape, size, and function. Physics-based models defining the subcellular force distribution facilitate this, but it is challenging to calibrate parameters in these models from data. To solve this inverse problem, we created a Bayesian optimization framework to determine the optimal cellular force distribution such that the predicted organ shapes match the experimentally observed organ shapes. This integrative framework employs Gaussian Process Regression, a non-parametric kernel-based probabilistic machine learning modeling paradigm, to learn the mapping functions relating to the morphogenetic programs that maintain the final organ shape. We calibrated and tested the method on Drosophila wing imaginal discs to study mechanisms that regulate epithelial processes ranging from development to cancer. The parameter estimation framework successfully infers the underlying changes in core parameters needed to match simulation data with imaging data of wing discs perturbed with collagenase. The computational pipeline identifies distinct parameter sets mimicking wild-type shapes. It enables a global sensitivity analysis to support the regulation of actomyosin contractility and basal ECM stiffness to generate and maintain the curved shape of the wing imaginal disc. The optimization framework, combined with experimental imaging, identified that Piezo, a mechanosensitive ion channel, impacts fold formation by regulating the apical-basal balance of actomyosin contractility and elasticity of ECM. This workflow is extensible toward reverse-engineering morphogenesis across organ systems and for real-time control of complex multicellular systems.

Indoor measurement and analysis on soil-traction device interaction using a soil bin

Investigating the mechanical interaction between vehicles and soil requires measuring various mechanical parameters, which have been enhanced through the advancement of measurement tools. This study delves into the measurement tools and data recording devices utilized in soil-traction device studies conducted at the Off-Road Vehicle Research Center of Urmia University. The tools and methods used for measuring and recording parameters such as forces, velocities, displacements, stresses, and contact areas during traction engagements of laboratory test traction devices (wheels and tracks) are presented. These measurements may have been simultaneously obtained using multiple transducers. The results demonstrate the data acquisition system's successful measurement and recording of these parameters. This research emphasizes the integration of different sensors, developing and implementing a unified data acquisition system for various transducers, and creating innovative setups for measuring and recording parameters such as soil density and wheel-soil contact area, which are of significant importance.

A Hydrodynamic‐Based Physical Unified Modeling for Simulating Shallow Landslide Local Failures, Mass Release and Debris Flow Run‐Out Extent Behavior

AbstractAccurate prediction of shallow landslide occurrence and the subsequent motion range after transformation into debris flows is crucial for reducing disaster‐induced losses. The use of Cellular Automata‐based (CA) hydrodynamic models has seen increasing application in predicting landslides, debris flows, and other related hazards. However, previous CA‐based models have primarily focused on the motion and evolution process of debris flows, lacking detailed description about the dynamic instability associated with shallow landslides. In this study, we propose a comprehensive CA‐based model that is based on existing theories and improved models for simulating hydrological processes, sliding surface identification algorithms, threshold‐based mechanical interactions, material entrainment, and deposition. The model was applied to the Yindongzi (YDZ) landslides in Sichuan, China. The accuracy of the model was validated through comparisons with field investigation results and calculations based on shallow water equations. This model enables efficient and rapid prediction of shallow landslide occurrence time, volume, spatial distribution, and runout distance. Evaluation of the model’s predictive performance reveals an error range of −23.12% to +44.26% for YDZ landslides. Moreover, the influence of different shallow landslide failure patterns on the deposition and erosion of debris flows was analyzed. The results indicate that the failure patterns of shallow landslides significantly affect the deposition and entrainment capacity of debris flows. This study provides a novel approach for predicting the occurrence of shallow landslides and the subsequent motion, entrainment, and deposition after transformation into debris flows.

The Yannoe Force in the Mechanics of “Aspin Bubbles”

"Aspin Bubbles" is a theory that obtains all known forces (electric, gravity, nuclear, Casimir...) based on a single mechanical interaction between waves and particles that make up our matter. The most surprising thing is that it demonstrates that the force of the gravity is a consequence of the sum of all the electrical forces existing between two neutral materials. In addition, "Aspin Bubbles" opens the door to new knowledge with the obtaining of a force not yet detected that it calls "Yannoe force", and with it, explains phenomena such as the levitation of clouds, dark matter, dark energy and the accelerated expansion of our universe

Polarised cell intercalation during Drosophila axis extension is robust to an orthogonal pull by the invaginating mesoderm.

As tissues grow and change shape during animal development, they physically pull and push on each other, and these mechanical interactions can be important for morphogenesis. During Drosophila gastrulation, mesoderm invagination temporally overlaps with the convergence and extension of the ectodermal germband; the latter is caused primarily by Myosin II-driven polarised cell intercalation. Here, we investigate the impact of mesoderm invagination on ectoderm extension, examining possible mechanical and mechanotransductive effects on Myosin II recruitment and polarised cell intercalation. We find that the germband ectoderm is deformed by the mesoderm pulling in the orthogonal direction to germband extension (GBE), showing mechanical coupling between these tissues. However, we do not find a significant change in Myosin II planar polarisation in response to mesoderm invagination, nor in the rate of junction shrinkage leading to neighbour exchange events. We conclude that the main cellular mechanism of axis extension, polarised cell intercalation, is robust to the mesoderm invagination pull. We find, however, that mesoderm invagination slows down the rate of anterior-posterior cell elongation that contributes to axis extension, counteracting the tension from the endoderm invagination, which pulls along the direction of GBE.

Ultimately Adaptive Fluid Interfacial Phospholipid Membranes Unveiled Unanticipated High Cellular Mechanical Work.

Living cells actively interact biochemically and mechanically with the surrounding extracellular matrices (ECMs) and undergo dramatic morphological and dimensional transitions, concomitantly remodeling ECMs. However, there is no suitable method to quantitatively discuss the contribution of mechanical interactions in such mutually adaptive processes. Herein, a highly deformable "living" cellular scaffold is developed to evaluate overall mechanical energy transfer between cell and ECMs. It is based on the water-perfluorocarbon interface decorated with phospholipids bearing a cell-adhesive ligand and fluorescent tag. The bioinert nature of the phospholipid membranes prevents the formation of solid-like protein nanofilms at the fluid interface, enabling to visualize and quantify cellular mechanical work against the ultimately adaptive model ECM. A new cellular wetting regime is identified, wherein interface deformation proceeds to cell flattening, followed by its eventual restoration. The cellular mechanical work during this adaptive wetting process is one order of magnitude higher than those reported withconventional elastic platforms. The behavior of viscous liquid drops at the air-water interface can simulate cellular adaptive wetting, suggesting that overall viscoelasticity of the cell body predominates the emergent wetting regime and regulates mechanical output. Cellular-force-driven high-energy states on the adaptive platform can be useful for cell fate manipulation.

Effect of absolute blood volume measurement-guided fluid management on the incidence of intradialytic hypotension-associated events: a randomised controlled trial.

Ultrafiltration to target weight during haemodialysis is complicated by intradialytic hypotension-associated adverse events (IHAAEs) in 10-30% of dialysis treatments. IHAAEs are caused by critical reductions in absolute blood volume (ABV), due to the interaction of ultrafiltration, refill and compensatory mechanisms. Non-randomised studies have suggested that ABV-guided treatment, using an indicator dilution technique employing the blood volume monitor on the dialysis machine, could reduce the incidence of IHAAEs. We performed an open-label randomised controlled trial. Patients were randomly assigned to adjustment of target weight guided by ABV measurements or standard care. The primary outcome was the change in the incidence of IHAAEs from baseline, defined as the percentage of treatment episodes in a 4-week period where the patient had a systolic blood pressure <90mmHg or symptoms of impending hypotension. ABV measurements were compared with anthropomorphometric estimation and the gold standard using isotope dilution. A total of 56 patients were randomised, of whom 29 were allocated to ABV-guided treatment and 27 to standard care. Overall baseline incidence of IHAAEs was 26.0%. ABV-guided treatment significantly reduced the incidence of IHAAEs compared with standard care, with a mean change from baseline of -9.6% [95% confidence interval (CI) -17.3 to -1.8) versus 2.4% (95% CI -2.3-7.2). The adjusted difference between the groups was 10.5% (95% CI 1.3-19.8; P=.026). ABV measurement had moderate agreement with other methods to estimate blood volume. The sensitivity for the previously suggested threshold of a post-dialysis normalised blood volume of 65ml/kg was observed to be 74% in this study. ABV-guided volume management significantly reduced IHAAEs compared with standard care. The clinical relevance of the previously suggested threshold of 65ml/kg cannot be firmly concluded on the basis of our results. If confirmed in a larger trial, this intervention could potentially change dialysis practice and impact patient care in a clinically meaningful way.

Contact stiffness of the multi-indenter contact interface

Mechanical contact plays a pivotal role in both industrial and daily life applications. Contact stiffness of a multi-indenter contact interface fundamentally determines force–deformation relations. However, the understanding of the overall contact stiffness from the historical perspective is limited owing to inherent difficulties in precisely characterizing the interaction in multi-indenter contacts. In this study, the mechanical strong interaction among indenters is pinpointed. A theoretical model for accurately determining the contact stiffness of multi-indenter contact interface is developed. The physical mechanism of the contact stiffness of multi-indenter contact interface is revealed. The theoretical model is solidly validated by experiment and simulation. More importantly, the present theoretical model can predict the contact stiffness of contact interfaces with complex and irregular configurations, which may be filled up with indenters of hierarchical structures. The critical load is determined to guarantee the finished product rate during transfer printing. This is experimentally evidenced by the transfer printing of silicon wafers with complexly customized patterns. The present study provides a profound guidance for various engineering applications such as fabrication and integration of micro- and nano-electronic chips as well as electronic devices.

Phenotypic selection patterns in a hybrid zone between two Calceolaria species with contrasting pollinators: insights from field surveys and fitness assessments.

Hybrid zones provide natural experimental settings to test hypotheses about species divergence. We concentrated on a hybrid swarm in which oil-collecting bees and flower-pecking birds act as pollinators of two Calceolaria species. We asked whether both pollinators contributed to flower divergence by differentially promoting prezygotic fitness at the phenotypic extremes that represent parentals. We studied pollinator-mediated selection on phenotypic traits critical in plant-pollinator mechanical interaction, namely plant height, reward-to-stigma distance, and flower shape. We utilised the quantity and quality of pollen deposited as fitness measures and distinguished between the contribution of the two pollinator types. Results showed uni- and bivariate disruptive selection for most traits through pollen grains deposited by both pollinators. Bird-mediated fitness favoured low plants with a long reward-to-stigma distance and a straight corolla, while bee-mediated fitness favoured tall plants with a short reward-to-stigma distance and curved corolla. In addition, stabilising selection at one end of the phenotypic range showed a bird-mediated reproductive asymmetry within the swarm. The disruptive pattern was countered, albeit weakly, by hybrids receiving higher-quality pollen on the stigmas. Results suggest that pollinator-mediated selection promotes divergence of integrated flower phenotypes mechanically adjusted either to bees or birds underscoring the importance of pollinator specialisation in diversification.

Prediction of burden distribution and electrical resistance in submerged arc furnaces using discrete element method modelling

A computational model of a submerged arc furnace (SAF) used in the production of ferrochrome is presented. The model's intended use is to investigate the extent to which intrinsic and extrinsic properties of the raw materials affect burden distribution and electrical resistance within the furnace. The model is built on the discrete element method and calculates the mechanical interactions of particle distributions resulting from the flow motion of typical raw materials used in the smelting of chromium ore. This model excludes the effects of thermodynamics, furnace chemistry, and heat transfer. It illustrates how the consumption of materials (chromite pellets, flux, and reductant) is affected by changes in electrode length, reductant fractions, and reductant sizing and density during the formation of a reductant bed. The resistance calculation algorithm developed by Mintek was applied to construct networks developed from particle contacts, which can quantitatively generate estimates of the electrode-to-electrode and electrode-to-bath electrical conduction conditions.

Differentially Expressed Genes Identification of Kohlrabi Seedlings (Brassica oleracea var. caulorapa L.) under Polyethylene Glycol Osmotic Stress and AP2/ERF Transcription Factor Family Analysis.

Osmotic stress is a condition in which plants do not get enough water due to changes in environmental factors. Plant response to osmotic stress is a complex process involving the interaction of different stress-sensitive mechanisms. Differentially expressed genes and response mechanisms of kohlrabi have not been reported under osmotic stress. A total of 196,642 unigenes and 33,040 differentially expressed unigenes were identified in kohlrabi seedlings under polyethylene glycol osmotic stress. AP2/ERF, NAC and eight other transcription factor family members with a high degree of interaction with CAT and SOD antioxidant enzyme activity were identified. Subsequently, 151 AP2/ERF genes were identified and analyzed. Twelve conserved motifs were searched and all AP2/ERF genes were clustered into four groups. A total of 149 AP2/ERF genes were randomly distributed on the chromosome, and relative expression level analysis showed that BocAP2/ERF genes of kohlrabi have obvious specificity in different tissues. This study lays a foundation for explaining the osmotic stress resistance mechanism of kohlrabi and provides a theoretical basis for the functional analysis of BocAP2/ERF transcription factor family members.

MiRNA-Mediated Fine Regulation of TLR-Induced M1 Polarization.

Macrophage polarization to the M1 spectrum is induced by bacterial cell wall components through stimulation of Toll-like family (TLR) receptors. By orchestrating the expression of relevant mediators of the TLR cascade, as well as associated pathways and feedback loops, macrophage polarization is coordinated to ensure an appropriate immune response. This is central to the successful control of pathogens and the maintenance of health. Macrophage polarization is known to be modulated at both the transcriptional and post-transcriptional levels. In recent years, the miRNA-based post-transcriptional regulation of M1 polarization has received increasing attention from the scientific community. Comparative studies have shown that TLR stimulation alters the miRNA profile of macrophages and that macrophages from the M1 or the M2 spectrum differ in terms of miRNAs expressed. Simultaneously, miRNAs are considered critical post-transcriptional regulators of macrophage polarization. In particular, miRNAs are thought to play a regulatory role in the switch between the early proinflammatory response and the resolution phase. In this review, we will discuss the current state of knowledge on the complex interaction of transcriptional and post-transcriptional regulatory mechanisms that ultimately determine the functionality of macrophages.