Moving mass over a viscoelastic system: asymptotic behaviours and insights into nonlinear dynamics

Moving masses are of interest in many applications of structural dynamics, soliciting in the last decades a vast debate in the scientific literature. However, despite the attention devoted to the subject, to the best of the authors’ knowledge, there is a lack of analysis about the fate of a movable mass when it rolls or slips with friction on a structure. With the aim of elucidating the dynamics of the simplest paradigm of this system and to investigate its asymptotic response, we make reference to a two-degree-of-freedom model made of an elastically vibrating carriage surmounted by a spherical mass, facing the problem both theoretically and experimentally. In case of linear systems, the analytical solutions and the laboratory tests performed on ad hoc constructed prototypes highlighted a counterintuitive asymptotic dynamics, here called binary: in the absence of friction at the interface of the bodies’ system, the mass holds its initial position or, if nonzero damping acts, at the end of the motion it is in a position that exactly recovers the initial relative distance carriage–sphere. While the first result might be somewhat obvious, the second appears rather surprising. Such a binary behaviour is also confirmed for a Duffing-like system, equipped with cubic springs, while it can be lost when non-smooth friction phenomena occur, as well as in the case of elastic springs restraining the motion of the sphere. The obtained analytical results and the numerical findings, also confirmed by experimental evidences, contribute to the basic understanding of the role played by the damping parameters governing the systems’ dynamics with respect to its asymptotic behaviour and could pave the way for designing active or passive vibration controllers of interest in engineering

Growth and remodeling in highly stressed solid tumors

Growing biological media develop residual stresses to make compatible elastic and inelastic growth-induced deformations, which in turn remodel the tissue properties modifying the actual elastic moduli and transforming an initially isotropic and homogeneous material into a spatially inhomogeneous and anisotropic one. This process is crucial in solid tumor growth mechanobiology, the residual stresses directly influencing tumor aggressiveness, nutrients walkway, necrosis and angiogenesis. With this in mind, we here analyze the problem of a hyperelastic sphere undergoing finite heterogeneous growth, in cases of different boundary conditions and spherical symmetry. By following an analytical approach, we obtain the explicit expression of the tangent elasticity tensor at any point of the material body as a function of the prescribed growth, by involving a small-on-large procedure and exploiting exact solutions for layered media. The results allowed to gain several new insights into how growth-guided mechanical stresses and remodeling processes can influence the solid tumor development. In particular, we highlight that— under hypotheses consistent with mechanical and physiological conditions—auxetic (negative Poisson ratio) transformations of the elastic response of selected growing mass districts could occur and contribute to explain some not yet completely understood phenomena associated to solid tumors. The general approach proposed in the present work could be also helpfully employed to conceive composite materials where ad hoc pre-stress distributions can be designed to obtain auxetic or other selected mechanical properties

Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44.

Sulfatase modifying factor 1 (SUMF1) encodes for the formylglicine generating enzyme, which activates sulfatases by modifying a key cysteine residue within their catalytic domains. SUMF1 is mutated in patients affected by multiple sulfatase deficiency, a rare recessive disorder in which all sulfatase activities are impaired. Despite the absence of canonical retention/retrieval signals, SUMF1 is largely retained in the endoplasmic reticulum (ER), where it exerts its enzymatic activity on nascent sulfatases. Part of SUMF1 is secreted and paracrinally taken up by distant cells. Here we show that SUMF1 interacts with protein disulfide isomerase (PDI) and ERp44, two thioredoxin family members residing in the early secretory pathway, and with ERGIC-53, a lectin that shuttles between the ER and the Golgi. Functional assays reveal that these interactions are crucial for controlling SUMF1 traffic and function. PDI couples SUMF1 retention and activation in the ER. ERGIC-53 and ERp44 act downstream, favoring SUMF1 export from and retrieval to the ER, respectively. Silencing ERGIC-53 causes proteasomal degradation of SUMF1, while down-regulating ERp44 promotes its secretion. When over-expressed, each of three interactors favors intracellular accumulation. Our results reveal a multistep control of SUMF1 trafficking, with sequential interactions dynamically determining ER localization, activity and secretion

Digital holography as 3D tracking tool for assessing acoustophoretic particle manipulation

The integration of digital holography (DH) imaging and the acoustic manipulation of micro-particles in a microfluidic environment is investigated. The ability of DH to provide efficient 3D tracking of particles inside a microfluidic channel is exploited to measure the position of multiple objects moving under the effect of stationary ultrasound pressure fields. The axial displacement provides a direct verification of the numerically computed positions of the standing wave’s node, while the particle’s transversal movement highlights the presence of nodes in the planar direction. Moreover, DH is used to follow the aggregation dynamics of trapped spheres in such nodes by using aggregation rate metrics

Symmetry breaking and effects of nutrient walkway in time-dependent bone remodeling incorporating poroelasticity

© 2022. The Author(s).Bone is an extraordinary biological material that continuously adapts its hierarchical microstructure to respond to static and dynamic loads for offering optimal mechanical features, in terms of stiffness and toughness, across different scales, from the sub-microscopic constituents within osteons-where the cyclic activity of osteoblasts, osteoclasts, and osteocytes redesigns shape and percentage of mineral crystals and collagen fibers-up to the macroscopic level, with growth and remodeling processes that modify the architecture of both compact and porous bone districts. Despite the intrinsic complexity of the bone mechanobiology, involving coupling phenomena of micro-damage, nutrients supply driven by fluid flowing throughout hierarchical networks, and cells turnover, successful models and numerical algorithms have been presented in the literature to predict, at the macroscale, how bone remodels under mechanical stimuli, a fundamental issue in many medical applications such as optimization of femur prostheses and diagnosis of the risk fracture. Within this framework, one of the most classical strategies employed in the studies is the so-called Stanford's law, which allows uploading the effect of the time-dependent load-induced stress stimulus into a biomechanical model to guess the bone structure evolution. In the present work, we generalize this approach by introducing the bone poroelasticity, thus incorporating in the model the role of the fluid content that, by driving nutrients and contributing to the removal of wastes of bone tissue cells, synergistically interacts with the classical stress fields to change homeostasis states, local saturation conditions, and reorients the bone density rate, in this way affecting growth and remodeling. Through two paradigmatic example applications, i.e. a cylindrical slice with internal prescribed displacements idealizing a tract of femoral diaphysis pushed out by the pressure exerted by a femur prosthesis and a bone element in a form of a bent beam, it is highlighted that the present model is capable to catch more realistically both the transition between spongy and cortical regions and the expected non-symmetrical evolution of bone tissue density in the medium-long term, unpredictable with the standard approach. A real study case of a femur is also considered at the end in order to show the effectiveness of the proposed remodeling algorithm.Peer reviewe

Growth and in vivo stresses traced through tumor mechanics enriched with predator-prey cells dynamics

Mechanical stress accumulating during growth in solid tumors plays a crucial role in the tumor mechanobiology. Stresses arise as a consequence of the spatially inhomogeneous tissue growth due to the different activity of healthy and cancer cells inhabiting the various districts of the tissue, an additional piling up effect, induced by stress transferring across the scales, contributing to determine the total stress occurring at the macroscopic level. The spatially inhomogeneous growth rates accompany nonuniform and time-propagating stress profiles, which constitute mechanical barriers to nutrient transport and influence the intratumoral interstitial flow, in this way deciding the starved/feeded regions, with direct aftereffects on necrosis, angiogenesis, cancer aggressiveness and overall tumor mass size. Despite their ascertained role in tumor mechanobiology, stresses cannot be directly appraised neither from overall tumor size nor through standard non-invasive measurements. To date, the sole way for qualitatively revealing their presence within solid tumors is ex vivo, by engraving the excised masses and then observing opening between the cut edges. Therefore, to contribute to unveil stresses and their implications in tumors, it is first proposed a multiscale model where Volterra-Lotka (predator/prey–like) equations describing the interspecific (environment-mediated) competitions among healthy and cancer cells are coupled with equations of nonlinear poroelasticity. Then, an experimental study on mice injected subcutaneously with a suspension of two different cancer cell lines (MiaPaCa-2 and MDA.MB231) was conducted to provide experimental evidences that gave qualitative and some new quantitative confirmations of the theoretical model predictions

Simulating the ideal geometrical and biomechanical parameters of the pulmonary autograft to prevent failure in the Ross operation

OBJECTIVES: Reinforcements for the pulmonary autograft (PA) in the Ross operation have been introduced to avoid the drawback of conduit expansion and failure. With the aid of an in silico simulation, the biomechanical boundaries applied to a healthy PA during the operation were studied to tailor the best implant technique to prevent reoperation. METHODS: Follow-up echocardiograms of 66 Ross procedures were reviewed. Changes in the dimensions and geometry of reinforced and non-reinforced PAs were evaluated. Miniroot and subcoronary implantation techniques were used in this series. Mechanical stress tests were performed on 36 human pulmonary and aortic roots explanted from donor hearts. Finite element analysis was applied to obtain high-fidelity simulation under static and dynamic conditions of the biomechanical properties and applied stresses on the PA root and leaflet and the similar components of the native aorta. RESULTS: The non-reinforced group showed increases in the percentages of the mean diameter that were significantly higher than those in the reinforced group at the level of the Valsalva sinuses (3.9%) and the annulus (12.1%). The mechanical simulation confirmed geometrical and dimensional changes detected by clinical imaging and demonstrated the non-linear biomechanical behaviour of the PA anastomosed to the aorta, a stiffer behaviour of the aortic root in relation to the PA and similar qualitative and quantitative behaviours of leaflets of the 2 tissues. The annulus was the most significant constraint to dilation and affected the distribution of stress and strain within the entire complex, with particular strain on the sutured regions. The PA was able to evenly absorb mechanical stresses but was less adaptable to circumferential stresses, potentially explaining its known dilatation tendency over time. CONCLUSIONS: The absence of reinforcement leads to a more marked increase in the diameter of the PA. Preservation of the native geometry of the PA root is crucial; the miniroot technique with external reinforcement is the most suitable strategy in this context

Phosphorylation-regulated degradation of the tumor-suppressor form of PED by chaperone-mediated autophagy in lung cancer cells

PED/PEA-15 is a death effector domain (DED) family member with a variety of effects on cell growth and metabolism. To get further insight into the role of PED in cancer, we aimed to find new PED interactors. Using tandem affinity purification, we identified HSC70 (Heat Shock Cognate Protein of 70kDa)-which, among other processes, is involved in chaperone-mediated autophagy (CMA)-as a PED-interacting protein. We found that PED has two CMA-like motifs (i.e., KFERQ), one of which is located within a phosphorylation site, and demonstrate that PED is a bona fide CMA substrate and the first example in which phosphorylation modifies the ability of HSC70 to access KFERQ-like motifs and target the protein for lysosomal degradation. Phosphorylation of PED switches its function from tumor suppression to tumor promotion, and we show that HSC70 preferentially targets the unphosphorylated form of PED to CMA. Therefore, we propose that the up-regulated CMA activity characteristic of most types of cancer cell enhances oncogenesis by shifting the balance of PED function toward tumor promotion. This mechanism is consistent with the notion of a therapeutic potential for targeting CMA in cancer, as inhibition of this autophagic pathway may help restore a physiological ratio of PED form