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

Abstract

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 aforementioned 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.

In silico optical control of pinned electrical vortices in an excitable biological medium

“…Our results confirmed that the typical basin of attraction of a circular inhomogeneity, for both conduction-type and light-induced cases, is circular, provided the spiral was exposed to the inhomogeneity for a reasonably long time (>3 s) (see figure 3. At short timescales, while the basin of attraction for a conduction-type inhomogeneity remained circular, with lower average probability of attraction at shorter observation times, the basin of attraction of a light-induced inhomogeneity developped a bias, as in figure 3 of Majumder et al [8] indicating that brief light pulses could be used for directed attraction-based movement, as is required for AAD.…”

“…To this end, we first produced a stationary rotating vortex, pinned to a circular conductiontype inhomogeneity, in a simulated monolayer of neonatal rat cardiac atrial cells. Next, we created a circular light-induced inhomogeneity, close to the location of the anchored vortex, by applying a light spot to the in silico monolayer, as described in Majumder et al [8]. We observed unpinning of the anchored vortex from the conduction-type inhomogeneity, followed by its re-attachment to the light-induced inhomogeneity.…”

“…For decades, researchers have worked at developing control mechanisms for these reentrant waves in the heart. However, only recently, after the advent of cardiac optogenetics, a method to exert real-time spatiotemporal control over spiral wave dynamics by targeting an area close to the core of the vortex, was proposed [8]. Arrhythmias driven by pinned spiral (scroll) waves are extremely important in cardiology.…”

“…The important features of the vortex, such as, the rotation frequency, spatial organization of emitted waves are determined by a core of a vortex, which is characterized by a phase singularity point, or a closed loop of phase singularities. It was shown that real-time manipulation of the core, could result in direct spatiotemporal control over these vortices in various excitable systems [8][9][10]. However, these studies focused on controlling vortices that existed freely in the medium, without attaching to a physical inhomogeneity.…”

“…Recently Majumderet al [8] proposed a novel method to control spiral waves in cardiac tissue. They demonstrated realtime spatiotemporal control over spiral wave dynamics by pinning-based relocation of vortices in optogenetically-modified monolayers of neonatal rat cardiac cells.…”