Micromachined Tools Using Acoustic Wave Triggering for the Interaction with the Growth of Plant Biological Systems.

A plant biological system is exposed to external influences. In general, each plant has its characteristics and needs with specific interaction mechanisms adapted to its survival. Interactions between systems can be examined and modeled as energy exchanges of mechanical, chemical or electrical variables. Thus, each specific interaction can be examined by triggering the system via a specific stimulus. The objective of this work was to study a specific stimulus (mechanical stimulation) as a driver of plants and their interaction with the environment. In particular, the experimental design concerns the setting up and testing of an automatic source of mechanical stimuli at different wavelengths, generated by an electromechanical transducer, to induce a micro-interaction in plants (or in parts of them) that produces a specific behavior (hypothesis) of plants. Four different experimental setups were developed for this work, each pursuing the same objective: the analysis of the germination process induced by stimulation by sound waves in the audible range. It can be said that the introduction of sound waves as a stimulant or a brake for the growth of plants can offer significant advantages when used on a large scale in the primary sector, since these effects can be used instead of polluting chemical solutions.

Thermal effects on cardiac alternans onset and development: A spatiotemporal correlation analysis.

Alternans of cardiac action potential duration represent critical precursors for the development of life-threatening arrhythmias and sudden cardiac death. The system's thermal state affects these electrical disorders requiring additional theoretical and experimental efforts to improve a patient-specific clinical understanding. In such a scenario, we generalize a recent work from Loppini et al. [Phys. Rev. E 100, 020201(R) (2019)PREHBM2470-004510.1103/PhysRevE.100.020201] by performing an extended spatiotemporal correlation study. We consider high-resolution optical mapping recordings of canine ventricular wedges' electrical activity at different temperatures and pacing frequencies. We aim to recommend the extracted characteristic length as a potential predictive index of cardiac alternans onset and evolution within a wide range of system states. In particular, we show that a reduction of temperature results in a drop of the characteristic length, confirming the impact of thermal instabilities on cardiac dynamics. Moreover, we theoretically investigate the use of such an index to identify and predict different alternans regimes. Finally, we propose a constitutive phenomenological law linking conduction velocity, characteristic length, and temperature in view of future numerical investigations.

Breaking down calcium timing in heterogenous cells populations.

Calcium controls a large number of cellular processes at different scales. Decades of studies have pointed out the importance of calcium signaling in regulating differentiation, apoptosis, mitosis and functions such as secretion, muscle contraction and memory. The space-time structure of calcium signaling is central to this complex regulation. In particular, cells within organisms behave as clocks beating their own biological time, although in several cases they can synchronize across long distances leading to an emergent space-time dynamics which is central for single cell and organ functioning. We use a mathematical model built on published experimental data of hepatic non-excitable cells, analyzing emerging calcium dynamics of cells clusters composed both of normally functioning cells and pathological aggregates. Calcium oscillations are investigated by varying the severity of dysfunction and size of pathological aggregate. We show how strong and localized heterogeneity in cellular properties can profoundly alter organized calcium dynamics leading to sub-populations of cells which create their own coordinated dynamical organization. Our simulations of Ca2+ signals reveal how cell behaviors differ and are related to intrinsic time signals. Such different cells clusters dynamically influence each other so that non-physiological although organized calcium patterns are generated. This new reorganization of calcium activity may possibly be a precursor of cancer initiation.

Spatiotemporal correlation uncovers characteristic lengths in cardiac tissue.

Complex spatiotemporal patterns of action potential duration have been shown to occur in many mammalian hearts due to period-doubling bifurcations that develop with increasing frequency of stimulation. Here, through high-resolution optical mapping experiments and mathematical modeling, we introduce a characteristic spatial length of cardiac activity in canine ventricular wedges via a spatiotemporal correlation analysis, at different stimulation frequencies and during fibrillation. We show that the characteristic length ranges from 40 to 20 cm during one-to-one responses and it decreases to a specific value of about 3 cm at the transition from period-doubling bifurcation to fibrillation. We further show that during fibrillation, the characteristic length is about 1 cm. Another significant outcome of our analysis is the finding of a constitutive phenomenological law obtained from a nonlinear fitting of experimental data which relates the conduction velocity restitution curve with the characteristic length of the system. The fractional exponent of 3/2 in our phenomenological law is in agreement with the domain size remapping required to reproduce experimental fibrillation dynamics within a realistic cardiac domain via accurate mathematical models.

Competing Mechanisms of Stress-Assisted Diffusivity and Stretch-Activated Currents in Cardiac Electromechanics.

We numerically investigate the role of mechanical stress in modifying the conductivity properties of cardiac tissue, and also assess the impact of these effects in the solutions generated by computational models for cardiac electromechanics. We follow the recent theoretical framework from Cherubini et al. (2017), proposed in the context of general reaction-diffusion-mechanics systems emerging from multiphysics continuum mechanics and finite elasticity. In the present study, the adapted models are compared against preliminary experimental data of pig right ventricle fluorescence optical mapping. These data contribute to the characterization of the observed inhomogeneity and anisotropy properties that result from mechanical deformation. Our novel approach simultaneously incorporates two mechanisms for mechano-electric feedback (MEF): stretch-activated currents (SAC) and stress-assisted diffusion (SAD); and we also identify their influence into the nonlinear spatiotemporal dynamics. It is found that (i) only specific combinations of the two MEF effects allow proper conduction velocity measurement; (ii) expected heterogeneities and anisotropies are obtained via the novel stress-assisted diffusion mechanisms; (iii) spiral wave meandering and drifting is highly mediated by the applied mechanical loading. We provide an analysis of the intrinsic structure of the nonlinear coupling mechanisms using computational tests conducted with finite element methods. In particular, we compare static and dynamic deformation regimes in the onset of cardiac arrhythmias and address other potential biomedical applications.

Systems Biology Modeling of Nonlinear Cancer Dynamics.

Systems Biology represents nowadays a promising standard framework for natural and human sciences to attack complicated problems involving Life. Here a particular application of such a program is discussed in the case of Cancer, by using a basic toy model for solid tumor spread for framing together two apparently different conceptual leading paradigms of Oncogenesis.

A note on stress-driven anisotropic diffusion and its role in active deformable media.

We introduce a new model to describe diffusion processes within active deformable media. Our general theoretical framework is based on physical and mathematical considerations, and it suggests to employ diffusion tensors directly influenced by the coupling with mechanical stress. The proposed generalised reaction-diffusion-mechanics model reveals that initially isotropic and homogeneous diffusion tensors turn into inhomogeneous and anisotropic quantities due to the intrinsic structure of the nonlinear coupling. We study the physical properties leading to these effects, and investigate mathematical conditions for its occurrence. Together, the mathematical model and the numerical results obtained using a mixed-primal finite element method, clearly support relevant consequences of stress-driven diffusion into anisotropy patterns, drifting, and conduction velocity of the resulting excitation waves. Our findings also indicate the applicability of this novel approach in the description of mechano-electric feedback in actively deforming bio-materials such as the cardiac tissue.

Computationally Informed Design of a Multi-Axial Actuated Microfluidic Chip Device.

This paper describes the computationally informed design and experimental validation of a microfluidic chip device with multi-axial stretching capabilities. The device, based on PDMS soft-lithography, consisted of a thin porous membrane, mounted between two fluidic compartments, and tensioned via a set of vacuum-driven actuators. A finite element analysis solver implementing a set of different nonlinear elastic and hyperelastic material models was used to drive the design and optimization of chip geometry and to investigate the resulting deformation patterns under multi-axial loading. Computational results were cross-validated by experimental testing of prototypal devices featuring the in silico optimized geometry. The proposed methodology represents a suite of computationally handy simulation tools that might find application in the design and in silico mechanical characterization of a wide range of stretchable microfluidic devices.

Role of topology in complex functional networks of beta cells.

The activity of pancreatic ß cells can be described by biological networks of coupled nonlinear oscillators that, via electrochemical synchronization, release insulin in response to augmented glucose levels. In this work, we analyze the emergent behavior of regular and percolated ß-cells clusters through a stochastic mathematical model where "functional" networks arise. We show that the emergence and robustness of the synchronized dynamics depend both on intrinsic and extrinsic parameters. In particular, cellular noise level, glucose concentration, network spatial architecture, and cell-to-cell coupling strength are the key factors for the generation of a rhythmic and robust activity. Their role in the functional network topology associated with ß-cells clusters is analyzed and discussed.

The role of coherence in emergent behavior of biological systems.

In his research activity, Emilio Del Giudice explored the possibility to move towards a unified view of some long-range dynamics in nature, ranging from quantum field theory in physics up to biology. Such a view is adopted in this contribution by discussing a mathematical model for synchronized electrical behavior of pancreatic beta cells. The stochasticity is a fundamental component of the physiological synchronized behavior of this system. On the contrary, in a pathological type I diabetes scenario, the cells are destroyed by the autoimmune system and their coherent behavior is lost. This phenomenology conceptually links to ideas of coherent dynamics in quantum physics. Possible implications both for physical sciences and for the epistemology of life sciences are outlined.

Mechanistic insights into hypothermic ventricular fibrillation: the role of temperature and tissue size.

AIMS: Hypothermia is well known to be pro-arrhythmic, yet it has beneficial effects as a resuscitation therapy and valuable during intracardiac surgeries. Therefore, we aim to study the mechanisms that induce fibrillation during hypothermia. A better understanding of the complex spatiotemporal dynamics of heart tissue as a function of temperature will be useful in managing the benefits and risks of hypothermia. METHODS AND RESULTS: We perform two-dimensional numerical simulations by using a minimal model of cardiac action potential propagation fine-tuned on experimental measurements. The model includes thermal factors acting on the ionic currents and the gating variables to correctly reproduce experimentally recorded restitution curves at different temperatures. Simulations are implemented using WebGL, which allows long simulations to be performed as they run close to real time. We describe (i) why fibrillation is easier to induce at low temperatures, (ii) that there is a minimum size required for fibrillation that depends on temperature, (iii) why the frequency of fibrillation decreases with decreasing temperature, and (iv) that regional cooling may be an anti-arrhythmic therapy for small tissue sizes however it may be pro-arrhythmic for large tissue sizes. CONCLUSION: Using a mathematical cardiac cell model, we are able to reproduce experimental observations, quantitative experimental results, and discuss possible mechanisms and implications of electrophysiological changes during hypothermia.

Mathematical modelling of active contraction in isolated cardiomyocytes.

We investigate the interaction of intracellular calcium spatio-temporal variations with the self-sustained contractions in cardiac myocytes. A consistent mathematical model is presented considering a hyperelastic description of the passive mechanical properties of the cell, combined with an active-strain framework to explain the active shortening of myocytes and its coupling with cytosolic and sarcoplasmic calcium dynamics. A finite element method based on a Taylor-Hood discretization is employed to approximate the nonlinear elasticity equations, whereas the calcium concentration and mechanical activation variables are discretized by piecewise linear finite elements. Several numerical tests illustrate the ability of the model in predicting key experimentally established characteristics including: (i) calcium propagation patterns and contractility, (ii) the influence of boundary conditions and cell shape on the onset of structural and active anisotropy and (iii) the high localized stress distributions at the focal adhesions. Besides, they also highlight the potential of the method in elucidating some important subcellular mechanisms affecting, e.g. cardiac repolarization.

Role of temperature on nonlinear cardiac dynamics.

Thermal effects affecting spatiotemporal behavior of cardiac tissue are discussed by relating temperature variations to proarrhythmic dynamics in the heart. By introducing a thermoelectric coupling in a minimal model of cardiac tissue, we are able to reproduce experimentally measured dynamics obtained simultaneously from epicardial and endocardial canine right ventricles at different temperatures. A quantitative description of emergent proarrhythmic properties of restitution, conduction velocity, and alternans regimes as a function of temperature is presented. Complex discordant alternans patterns that enhance tissue dispersion consisting of one wave front and three wave backs are described in both simulations and experiments. Possible implications for model generalization are finally discussed.

Wave-train-induced termination of weakly anchored vortices in excitable media.

A free vortex in excitable media can be displaced and removed by a wave train. However, simple physical arguments suggest that vortices anchored to large inexcitable obstacles cannot be removed similarly. We show that unpinning of vortices attached to obstacles smaller than the core radius of the free vortex is possible through pacing. The wave-train frequency necessary for unpinning increases with the obstacle size and we present a geometric explanation of this dependence. Our model-independent results suggest that decreasing excitability of the medium can facilitate pacing-induced removal of vortices in cardiac tissue.