Biology subjects

Avril, S.

Publications and source records attributed to Avril, S..

9 recordsLinked to original sources

bioRxiv2026

Feasibility study of fluid-structure-growth modelling in the context of endogenous tissue restoration

In situ tissue engineering exploits natural inflammatory responses to turn a synthetic vascular graft into a regenerated, functioning, and living vessel through endogenous tissue restoration. Despite promising preclinical results, challenges remain, especially in high-pressure regimes. To better understand the underlying biological processes and predict long-term outcomes of graft implantation, we propose an in silico approach. We account for the solid mechanics of conduit grafts in high and low pressure regimes, the wall shear stresses, and long-term growth and remodeling through two reduced-order fluid-structure-growth models. The first employs an artificial neural network surrogate model to compute the time-averaged wall shear stress at every growth step, whereas the second evaluates a fully-coupled fluid-structure interaction model every 60 time steps. We thoroughly verify both models and confirm acceptable model-form errors, then calibrate them against data from animal experiments. A validation study comparing in silico predictions with unseen animal data of carotid and pulmonary conduit grafts confirms that the model remains reliable up to at least one month of prediction time, hence in the future enabling in silico optimization of short-term endogenous tissue restoration in tissue engineering vascular grafts.

bioengineering↗

bioRxiv2026

The king of stress? Exploring the physiological resilience and resistance of adult king penguins to chronic glucocorticoid exposure

To better understand how animals cope with increasingly variable and challenging environments, there is a need to study how prolonged exposure to elevated glucocorticoid hormones (i.e. one mediator of the stress response) affects their physiology. While glucocorticoid elevation is known to increase oxidative stress and accelerate cellular ageing, there is evidence that king penguins (Aptenodytes patagonicus) can prevent oxidative stress during acute stress exposure, suggesting that species may differ in their sensitivity to glucocorticoids downstream negative effects. As king penguins thrive in a seemingly harsh environment, we hypothesized that they may be able to limit the deleterious effects usually associated with chronic glucocorticoid elevation, either through resistance (i.e. prevention of downstream negative effect) or resilience (i.e. rapid recovery following transient negative effect). To test this hypothesis, we experimentally elevated corticosterone levels in incubating king penguins and quantified treatment effects on a suite of physiological traits at multiple time points across incubation and early chick-rearing, up to ca. 2 months after implantation. Corticosterone-treated individuals showed a prolonged increase in corticosterone and decrease in body condition, confirming our treatment likely mimicked sustained stress exposure. Heterophil-to-lymphocyte ratio was only increased transiently, and there was no clear evidence that treatment influenced oxidative stress or telomere length maintenance. Plasma energy metabolites were mainly affected early after implantation, with rapid recovery over time. Overall, our results suggest that adult king penguins show at least moderate resistance and resilience to chronic corticosterone elevation, especially in preventing cellular integrity loss, though at-sea physiological effects remain to be determined.

physiology↗

bioRxiv2026

Granular Extracellular Matrix (gECM) Hydrogel Wafers as Shelf-Stable 2.5D Substrates for Microphysiological Modeling

Understanding disease pathology and evaluating emerging therapeutics require in vitro models that accurately recapitulate human tissue environments. However, existing microphysiological systems often compromise either biomimicry or ease-of-use, limiting widespread adoption and scalability. Here, we present lyophilized granular extracellular matrix (gECM) hydrogel wafers as shelf-stable, humanized 2.5D substrates that enable physiologically relevant modeling while simplifying integration into experimental workflows. Derived from decellularized human cartilage and bone, gECM hydrogel wafers retain tissue-specific architecture while introducing microporosity and surface topography through lyophilization. These wafers maintain swelling behavior, structural integrity, and mechanical properties over three months of room-temperature storage, allowing pre-fabrication and on-demand use without loss of function. gECM hydrogel wafers support direct cell seeding without encapsulation and sustain viability and proliferation of human adipose-derived mesenchymal stromal cells over 21 days, with gene expression trends comparable to 3D gECM hydrogels. Furthermore, wafers can be readily integrated into microfluidic systems with in situ hydration and transport of large biomolecules. Together, this platform bridges the gap between conventional 2D culture ease-of-use and 3D biomaterial biomimicry, providing a scalable and physiologically relevant in vitro model approach for high-throughput disease studies and therapeutic screening.

bioengineering↗

bioRxiv2025

A biomathematical approaches models to identify human platelet activation signature in response to various agonists

BackgroundPlatelets are crucial mediators at the crossroads of hemostasis, immunity, and inflammation, adapting their responses to diverse stimuli. Despite their recognized role, the precise pathways and markers associated with platelet activation remain poorly understood. This study aimed to unravel these mechanisms by evaluating platelet responses to various agonists, employing biomathematical models to map activation patterns and identify key biomarkers. MethodsUsing samples from ten healthy donors, platelets were exposed to seven stimulation conditions: unstimulated, PAR-1 agonist TRAP, PAR-4 agonist AYPGKF, ADP, collagen, sCD40L, and fibrinogen. A comprehensive analysis of 47 biological markers--covering membrane activation, soluble mediators, and signaling pathways--was conducted. Statistical and machine learning models, including hierarchical clustering and random forests, were applied to classify and interpret platelet activation signatures. ResultsDistinct activation profiles were observed for each agonist. A streamlined panel of six markers--AKT, CD40 ligand, CD62P (mean fluorescence intensity and percentage), PKC, RANTES, and TSLP--achieved 86.8% accuracy in identifying the activating stimulus. The study highlighted significant variations, influenced by both the stimulus and donor-specific factors. Machine learning approaches further refined classification, achieving a multiclass accuracy of 87.9%. Hierarchical clustering demonstrated clear distinctions, particularly between PAR-1/PAR-4 responses and other agonists. ConclusionThis innovative research redefines platelets as dynamic "biological sensors" capable of decoding complex danger signals. By integrating biomathematical modeling and artificial intelligence, it identifies a precise biomarker panel with transformative potential for diagnostics and therapies in inflammation and immune disorders. This work positions platelets not just as key players in hemostasis but as programmable agents for precision medicine, heralding a new era in adaptive, AI-driven healthcare solutions. Author SummaryPlatelets are often seen as simple players in blood clotting, but they do much more. They sit at the crossroads of hemostasis (stopping bleeding), innate immunity (our bodys first defense), and inflammation. They even influence adaptive immunity and play key roles in maintaining healthy blood vessels and contributing to disease. What makes platelets fascinating is their ability to respond quickly to their environment. They carry various receptors and release substances like growth factors, immune signals, clotting factors, RNA, and tiny vesicles. This helps them react to threats and communicate with other cells. But the big question is: can platelets tailor their response based on specific stimuli? In my research, I set out to answer this. Using mathematical models and analytical techniques, I studied how platelets react to different triggers, especially those linked to immune and clotting responses. My goal was to identify specific molecular "signatures" that define how platelets respond. I found that platelets can distinguish between danger signals and adjust their secretory responses. Normally, this helps manage threats efficiently. However, when this response exceeds whats needed, it can contribute to diseases like cardiovascular disorders, severe infections, autoimmune conditions, and cancer. Understanding these pathways opens new doors for treatment. Since platelet activity can be influenced by drugs, we could shift their role from harmful to beneficial in many diseases. This could revolutionize how we approach conditions driven by inflammation and immune dysregulation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/636809v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@9d9b5forg.highwire.dtl.DTLVardef@1438071org.highwire.dtl.DTLVardef@a59b29org.highwire.dtl.DTLVardef@6dd66b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

A synthetic elastic protein as molecular prosthetic candidate to strengthen vascular wall elasticity

The loss of elasticity is a hallmark of systemic aging or genetic syndromes (e.g. cutis laxa, Williams-Beuren and supravalvular aortic stenosis) with direct consequences on tissue functions, and particularly deleterious when associated to the cardiovascular system. Tissue elasticity is mainly provided by large elastic fibers composed of supramolecular complexes of elastin and microfibrils. In arteries, the mature elastic fibers are located in the media compartment and form concentric elastic lamellar units together with the smooth muscle cells (SMCs). The main function of vascular elastic fibers is to allow extension and recoil of the vessel walls in response to the intraluminal pressure generated by the blood flow following cardiac systole. The synthesis of elastic fibers (elastogenesis) mainly occurs during the last third of fetal life with a peak in the perinatal period and then slowly decreases until the end of growth; as a result, elastic fiber repair is almost non-existent in adults. To date, no treatment exists to restore or repair deficient or degraded elastic fibers. A few pharmacological compounds have been proposed, but their efficacy/side effects balance remains very unfavorable. As an alternative strategy, we developed a synthetic elastic protein (SEP) inspired by the human tropoelastin, the elastin soluble precursor, to provide an elastic molecular prosthesis capable of integrating and reinforcing endogenous elastic fibers. The SEP was easily produced in E. coli and purified by inversed transition cycling method. The resulting 55 kDa protein recapitulates the main physicochemical properties of the tropoelastin as thermal responsiveness, intrinsically disordered structures, and spherical self-assembly. The cross-linked SEP displays linear elastic mechanical properties under uniaxial tension loads. Using a co-culture in vitro model of the endothelial barrier, our results show that SEP is able to cross the cohesive endothelial monolayer to reach underlying SMCs. Moreover, SEP is processed by SMCs through a lysyl oxidase-dependent mechanism to form fibrillar structures that colocalize with fibrillin-rich microfibrils. The SEP was further characterized in vivo through the zebrafish model. The results indicate a global innocuity on zebrafish embryos and an absence of neutrophil recruitment following injection into the yolk sac of zebrafish. Finally, intravenous injection of a fluorescent SEP highlights its deposition in the wall of tortuous vessels which persists for several days after injection of the larvae. Taken together, our results demonstrate for the first time the incorporation of a naked tropoelastin-bioinspired polypeptide in endogenous elastic fibrillar deposits from SMCs, and its recognition by the lysyl- oxidase enzymatic machinery. In absence of toxicity and proinflammatory signal combined to a long-lasting accumulation in vessels in vivo, the SEP fulfills the first prerequisites for the development of an original biotherapeutic compound addressing the repair of elastic fibers.

cell biology↗

bioRxiv2023

Intervertebral Disc Elastography to Relate Shear Modulus and Relaxometry in Compression and Bending

Intervertebral disc degeneration is the most recognized cause of low back pain, characterized by the decline of tissue structure and mechanics. Image-based mechanical parameters (e.g., strain, stiffness) may provide an ideal assessment of disc function that is lost with degeneration but unfortunately remains underdeveloped. Moreover, it is unknown whether strain or stiffness of the disc may be predicted by MRI relaxometry (e.g. T1 or T2), an increasingly accepted quantitative measure of disc structure. In this study, we quantified T1 and T2 relaxation times and in-plane strains using displacement-encoded MRI within the disc under physiological levels of compression and bending. We then estimated shear modulus in orthogonal image planes and compared these values to relaxation times and strains within regions of the disc. Intratissue strain depended on the loading mode, and shear modulus in the nucleus pulposus was typically an order of magnitude lower than the annulus fibrosis, except in bending, where the apparent stiffness depended on the loading. Relative shear moduli estimated from strain data derived under compression generally did not correspond with those from bending experiments, with no correlations in the sagittal plane and only 4 of 15 regions correlated in the coronal plane, suggesting that future inverse models should incorporate multiple loading conditions. Strain imaging and strain-based estimation of material properties may serve as imaging biomarkers to distinguish healthy and diseased discs. Additionally, image-based elastography and relaxometry may be viewed as complementary measures of disc structure and function to assess degeneration in longitudinal studies.

bioengineering↗

bioRxiv2023

Surface temperatures are influenced by handling stress independently of glucocorticoid levels in wild king penguins

Assessing the physiological stress responses of wild animals opens a window for understanding how organisms cope with environmental challenges. Since stress response is associated with changes in body temperature, the use of body surface temperature through thermal imaging could help to measure acute and chronic stress responses non-invasively. We used thermal imaging, acute handling-stress protocol and an experimental manipulation of corticosterone (the main glucocorticoid hormone in birds) levels in breeding king penguins (Aptenodytes patagonicus), to assess: 1. the potential contribution of the Hypothalamo-Pituitary-Adrenal (HPA) axis in mediating chronic and acute stress-induced changes in adult surface temperature, 2. the influence of HPA axis manipulation on parental investment through thermal imaging of eggs and brooded chicks, and 3. the impact of parental treatment on offspring thermals response to acute handling. Maximum eye temperature (Teye) increased and minimum beak temperature (Tbeak) decreased in response to handling stress in adults, but neither basal nor stress-induced surface temperatures were significantly affected by corticosterone implant. While egg temperature was not significantly influenced by parental treatment, we found a surprising pattern for chicks: chicks brooded by the (non-implanted) partner of corticosterone-implanted individuals exhibited higher surface temperature (both Teye and Tbeak) than those brooded by glucocorticoid-implanted or control parents. Chicks response to handling in terms of surface temperature was characterized by a drop in both Teye and Tbeak independently of parental treatment. We conclude that the HPA axis seems unlikely to play a major role in determining chronic or acute changes in surface temperature in king penguins. Changes in surface temperature may primarily be mediated by the Sympathetic-Adrenal-Medullary (SAM) axis in response to stressful situations. Our experiment did not reveal a direct impact of parental HPA axis manipulation on parental investment (egg or chick temperature), but a potential influence on the partners brooding behaviour. HighlightsO_LIExperimental increase in corticosterone does not affect king penguins surface temperature C_LIO_LIAcute handling stress increases eye but decreases beak surface temperature in adults C_LIO_LIAcute handling decreases both eye and beak surface temperatures in young chicks C_LIO_LIParental corticosterone treatment does not affect egg surface temperature during incubation C_LIO_LIChicks brooded by non-implanted partners of corticosterone parents are warmer than chicks brooded by others adults. C_LI

zoology↗

bioRxiv2023

Stiffness Sensing by Smooth Muscle Cells:Continuum Mechanics Modeling of the Acto-Myosin Role

Aortic Smooth Muscle Cells (SMCs) play a vital role in maintaining homeostasis in the aorta by sensing and responding to mechanical stimuli. However, the mechanisms that underlie the ability of SMCs to sense and respond to stiffness change in their environment are still partially unclear. In this study, we focus on the role of acto-myosin contractility in stiffness sensing and introduce a novel continuum mechanics approach based on the principles of thermal strains. Each stress fiber satisfies a universal stress-strain relationship driven by a Youngs modulus, a contraction coefficient scaling the fictitious thermal strain, a maximum contraction stress and a softening parameter describing the sliding effects between actin and myosin filaments. To account for the inherent variability of cellular responses, large populations of SMCs are modeled with the finite-element method, each cell having a random number and a random arrangement of stress fibers. Moreover, the level of myosin activation in each stress fiber satisfies a Weibull probability density function. Model predictions are compared to traction force measurements on different SMC lineages. It is demonstrated that the model not only predicts well the effects of substrate stiffness on cellular traction, but it can also successfully approximate the statistical variations of cellular tractions induced by intercellular variability. Finally, stresses in the nuclear envelope and in the nucleus are computed with the model, showing that the variations of cytoskeletal forces induced by substrate stiffness directly induce deformations of the nucleus which can potentially alter gene expression. The predictability of the model combined to its relative simplicity are promising assets for further investigation of stiffness sensing in 3D environments. Eventually, this could contribute to decipher the effects of mechanosensitivity impairment, which are known to be at the root of aortic aneurysms.

biophysics↗

bioRxiv2021

General Finite-Element Framework of the Virtual Fields Method in Nonlinear Elasticity

This paper presents a method to derive the virtual fields for identifying constitutive model parameters using the Virtual Fields Method (VFM). The VFM is an approach to identify unknown constitutive parameters using deformation fields measured across a given volume of interest. The general principle for solving identification problems with the VFM is first to derive parametric stress field, where the stress components at any point depend on the unknown constitutive parameters, across the volume of interest from the measured deformation fields. Applying the principle of virtual work to the parametric stress fields, one can write scalar equations of the unknown parameters and solve the obtained system of equations to deduce the values of unknown parameters. However, no rules have been proposed to select the virtual fields in identification problems related to nonlinear elasticity and there are multiple strategies possible that can yield different results. In this work, we propose a systematic, robust and automatic approach to reconstruct the systems of scalar equations with the VFM. This approach is well suited to finite-element implementation and can be applied to any problem provided that full-field deformation data are available across a volume of interest. We also successfully demonstrate the feasibility of the novel approach by multiple numerical examples. Potential applications of the proposed approach are numerous in biomedical engineering where imaging techniques are commonly used to observe soft tissues and where alterations of material properties are markers of diseased states. List of symbols O_TBL View this table: org.highwire.dtl.DTLVardef@1addce2org.highwire.dtl.DTLVardef@1808699org.highwire.dtl.DTLVardef@104dadeorg.highwire.dtl.DTLVardef@1bd527aorg.highwire.dtl.DTLVardef@71ef75_HPS_FORMAT_FIGEXP M_TBL C_TBL

bioengineering↗