Wrinkling prediction, formation and evolution in thin films adhering on polymeric substrata

Wrinkling has recently attracted an increasing interest by suggesting a number of unforeseeable applications in many emerging material science and engineering fields. If guided and somehow designed, wrinkles could be in fact used as an alternative printing way for realizing complex surface geometries and thus employed as an innovative bottom-up process in the fabrication of nano- and micro-devices. For these reasons, the prediction of wrinkles of films adhering on flat as well as on structured substrata is a challenging task, genesis and development of the phenomenon being not yet completely understood both when thin membranes are coupled with soft supports and in cases where the geometry of the surfaces are characterized by complex three-dimensional profiles. Here we investigate the experimental formation of new intriguing and somehow unforeseeable wrinkled patterns achieved on periodic structures, by showing prediction through a new hybrid analytical-numerical strategy capable to overcome some common obstacles encountered in modeling film wrinkling on flat and 3D-shaped substrata. The proposed approach, which drastically reduces the computational effort, furnishes a helpful way for predicting both qualitative and quantitative results in terms of wrinkling patterns, magnitude and wavelength, by also allowing to follow the onset of film instabilities and the progressive evolution of the phenomenon until its final stage. Keywords: Thin film, Wrinkling, PDMS substrates, Lithium niobate crystals, FEM simulation

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

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

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

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

Stacking sequences in composite laminates through design optimization

AbstractComposites are experiencing a new era. The spatial resolution at which is to date possible to build up complex architectured microstructures through additive manufacturing-based and sintering of powder metals 3D printing techniques, as well as the recent improvements in both filament winding and automated fiber deposition processes, are opening new unforeseeable scenarios for applying optimization strategies to the design of high-performance structures and metamaterials that could previously be only theoretically conceived. Motivated by these new possibilities, the present work, by combining computational methods, analytical approaches and experimental analysis, shows how finite element Design Optimization algorithms can be ad hoc rewritten by identifying as design variables the orientation of the reinforcing fibers in each ply of a layered structure for redesigning fiber-reinforced composites exhibiting at the same time high stiffness and toughening, two features generally in competition each other. To highlight the flexibility and the effectiveness of the proposed strategy, after a brief recalling of the essential theoretical remarks and the implemented procedure, selected example applications are finally illustrated on laminated plates under different boundary conditions, cylindrical layered shells with varying curvature subjected to point loads and composite tubes made of carbon fiber-reinforced polymers, recently employed as structural components in advanced aerospace engineering applications

Inhibition of Tat activity by the HEXIM1 protein

BACKGROUND: The positive transcription elongation factor b (P-TEFb) composed by CDK9/CyclinT1 subunits is a dedicated co-factor of HIV transcriptional transactivator Tat protein. Transcription driven by the long terminal repeat (LTR) of HIV involves formation of a quaternary complex between P-TEFb, Tat and the TAR element. This recruitment is necessary to enhance the processivity of RNA Pol II from the HIV-1 5' LTR promoter. The activity of P-TEFb is regulated in vivo and in vitro by the HEXIM1/7SK snRNA ribonucleic-protein complex. RESULTS: Here we report that Tat transactivation is effectively inhibited by co-expression of HEXIM1 or its paralog HEXIM2. HEXIM1 expression specifically represses transcription mediated by the direct activation of P-TEFb through artificial recruitment of GAL4-CycT1. Using appropriate HEXIM1 mutants we determined that effective Tat-inhibition entails the 7SK snRNA basic recognition motif as well as the C-terminus region required for interaction with cyclin T1. Enhanced expression of HEXIM1 protein modestly affects P-TEFb activity, suggesting that HEXIM1-mediated repression of Tat activity is not due to a global inhibition of cellular transcription. CONCLUSION: These results point to a pivotal role of P-TEFb for Tat's optimal transcription activity and suggest that cellular proteins that regulate P-TEFb activity might exert profound effects on Tat function in vivo

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

Small-on-large fractional derivative-based single-cell model incorporating cytoskeleton prestretch

In the last years, experimental evidences have suggested important direct implications of vis-coelasticity of human cells and cell cytoskeleton dynamics on some relevant collective and at single cell behaviors such as migration, adhesion and morphogenesis. As a consequence, the me-chanical properties of single cells as well as how cells respond to mechanical stimuli have been –and currently are– at the center of a vivid debate in the scientific community. By making reference to important experimental findings from the literature which have shown that human metastatic tumor cells are about 70% softer than benign cells, independently from the cell lines examined, the present authors have very recently theoretically demonstrated that these differences in stiffness might be exploited to mechanically discriminate healthy and cancer cells, for example through low intensity therapeutic ultrasound. In particular, by means of a general-ized viscoelastic paradigm combining classical and fractional derivative-based models, it has been found that selected frequencies (from tens to hundreds kHz) are associated to resonance-like phe-nomena that are prevailing on thermal fluctuations and that could be hence, at least in principle, helpfully utilized for both targeting and selectively attacking tumor cells. With the aim of investigating the effect of the prestress –for instance induced in protein filaments during cell adhesion– on the overall cell stiffness and, in turn, on its in-frequency response, a simple multiscale scheme is here proposed to bottom-up enrich the spring-pot-based viscoelastic single-cell models, by incorporating finite elasticity and in this way determining, through sensitivity analyses, the role played by the stretched state of the cytoskeletal elements on the cell vibration