Biology subjects

de Vries, A. A. F.

Publications and source records attributed to de Vries, A. A. F..

4 recordsLinked to original sources

bioRxiv2025

Atypical collective oscillatory activity in cardiac tissue uncovered by optogenetics

Many biological processes emerge as frequency-dependent responses to trains of external stimuli. Heart rhythm disturbances, i.e. cardiac arrhythmias, are important examples as they are often triggered by specific patterns of preceding stimuli. In this study, we investigated how ectopic arrhythmias can be induced by external stimuli in cardiac tissue containing a localised area of depolarisation. Using optogenetic in vitro experiments and in silico modelling, we systematically explored the dynamics of these arrhythmias, which are characterized by local oscillatory activity, by gradually altering the degree of depolarization in a predefined region. Our findings reveal a bi-stable system, in which transitions between oscillatory ectopic activity and a quiescent state can be precisely controlled, i.e. by adjusting the number and frequency of propagating waves through the depolarized area oscillations could be turned on or off. These frequency-dependent responses arise from collective mechanisms involving stable, non-self-oscillatory cells, contrasting with the typical role of self-oscillations in individual units within biophysical systems. To further generalize these findings, we demonstrated similar frequency selectivity and bi-stability in a simplified reaction-diffusion model. This suggests that complex ionic cell dynamics are not required to reproduce these effects; rather, simpler non-linear systems can replicate similar behaviour, potentially extending beyond the cardiac context.

biophysics↗

bioRxiv2023

Optogenetic confirmation of transverse-tubular membrane excitability in intact cardiac myocytes

T-tubules (TT) form a complex network of sarcolemmal membrane invaginations, essential for well-coordinated excitation-contraction coupling (ECC) and, thus, homogeneous mechanical activation of cardiomyocytes. ECC is initiated by rapid depolarization of the sarcolemmal membrane. Whether TT membrane depolarisation is active (local generation of action potentials; AP) or passive (following depolarisation of the outer cell surface sarcolemma; SS) has not been experimentally assessed in cardiomyocytes. Based on the assessment of ion flux pathways needed for AP generation, we hypothesise that TT are excitable. We therefore explored TT excitability experimentally, using an all-optical approach to stimulate and record trans-membrane potential changes in TT that were electrically insulated from the SS membrane by transient osmotic shock. Our results establish that cardiomyocyte TT can generate AP. These AP show electrical features that differ substantially from those observed in SS, consistent with differences in the density of ion channels and transporters in the two different membrane domains. We propose that TT-generated AP represent a safety mechanism for TT AP propagation and ECC, which may be particularly relevant in pathophysiological settings where morpho-functional changes reduce the electrical connectivity between SS and TT membranes. KEY POINTSO_LICardiomyocytes are characterized by a complex network of membrane invaginations (the T-tubular system) that propagate action potentials to the core of the cell, ensuring synchronous and uniform cell contraction. C_LIO_LIIn this study, we investigate whether the T-tubular system is able to generate action potentials autonomously, rather than following depolarization of the outer cell surface sarcolemma. C_LIO_LIFor this purpose, we developed a fully optical platform to probe and manipulate the electrical dynamics of sub-cellular membrane domains. C_LIO_LIOur findings demonstrate that T-tubules are intrinsically excitable, revealing distinct characteristics of self-generated T-tubular action potentials. C_LIO_LIThis active electrical capability may serve as a protective mechanism against voltage drops occurring within the T-tubular network. C_LI

physiology↗

bioRxiv2023

Creation of predictive cardiac excitation models at the tissue scale with machine learning in augmented state space

The quick and easy creation of fast in-silico models of excitable media is, for instance, needed for patient-specific predictions in diagnostics and decision making in cardiac electrophysiology. We here present a model creation pipeline that not only generates new models quickly, but also only requires data from one easily measurable spatio-temporal variable. These data may, for instance, be an optical voltage mapping recording of the electrical waves in cardiac muscle tissue controlling the heart beat. We use exponential moving averages and compute standard deviations to extract additional states from this one variable to span a sparse discretised state space. The standard deviation in a neighbourhood can be used as a proxy for the gradient. To this augmented state space, we fit a simple polynomial model to predict the evolution of this one state variable. For optical voltage mapping data of human atrial myocyte monolayers electrically stimulated by stochastic burst pacing, the data-driven model is able to describe the excitation and recovery of the system, as well as wave propagation. The data-driven model is also able to predict spiral waves only based on data from focal waves. In contrast to conventional models, with our model creation pipeline new models can be generated in a matter of hours from experiment to fitting, rather than months or years. HighlightsO_LIModels of excitation waves can be created in minutes from experiment to fitting. C_LIO_LIOne variable in space and time is sufficient to create a working excitation model. C_LIO_LIA polynomial can predict excitation waves based on useful extracted features. C_LIO_LISpiral waves in heart muscle tissue can be predicted from focal wave data. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/540314v2_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@2165acorg.highwire.dtl.DTLVardef@9a1bfeorg.highwire.dtl.DTLVardef@1a3cd50org.highwire.dtl.DTLVardef@fc5698_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2018

Optogenetics enables real-time spatiotemporal control over spiral wave dynamics in an excitable cardiac system

Propagation of non-linear waves is key to the functioning of diverse biological systems. Such waves can organize into spirals, rotating around a core, whose properties determine the overall wave dynamics. Theoretically, manipulation of a spiral wave core should lead to full spatiotemporal control over its dynamics. However, this theory lacks supportive evidence (even at a conceptual level), making it thus a long-standing hypothesis. Here, we propose a new phenomenological concept that involves artificially dragging spiral waves by their cores, to prove the afore-mentioned hypothesis in silico, with subsequent in vitro validation in optogenetically-modified monolayers of rat atrial cardiomyocytes. We thereby connect previously established, but unrelated concepts of spiral wave attraction, anchoring and unpinning to demonstrate that core manipulation, through controlled displacement of heterogeneities in excitable media, allows forced movement of spiral waves along pre-defined trajectories. Consequently, we impose real-time spatiotemporal control over spiral wave dynamics in a biological system.

bioinformatics↗