A Bioelectric Failsafe: Spontaneous Symmetry-Breaking in Biology

In the study of biology, there is a lingering assumption that life is strictly dictated by a master genomic plan. We tend to view DNA as a highly detailed schematic with a set of coordinates telling every cell where to go and what to become.

Research in emergent complexity increasingly challenges these notions, showing that a genome is more of a parts list. DNA contains the instructions for manufacturing proteins, but it does not contain the geometric coordinates for where those proteins should be deployed. If you have a perfectly homogeneous sheet of genetically identical cells, how does the tissue know where to draw a line? How do identical cells, sitting in a uniform environment, agree to become different things to build a complex organ?

Once again, nature does not rely solely on a top-down master controller like the brain or the central dogma of DNA. Instead, it relies on the physics of symmetry-breaking to facilitate emergent complex order. Where the starfish embryo used fluid mechanics to build a macroscopic engine, homogeneous tissues use a different medium: bioelectricity.

Decoupling Electricity from the Brain

When we think of biological electricity, we immediately think of our nervous system and its rapid-firing spikes of neurons communicating across a brain. However, brains are a relatively recent evolutionary invention. Long before neurons existed, every cell on Earth possessed a resting membrane potential. Bioelectric signaling occurs almost everywhere in biology.

Every cell acts as a microscopic battery, using ion channels to pump charged particles across its membrane. This creates a voltage differential between the inside and the outside of the cell. For decades, this slow, resting bioelectricity was largely ignored as background noise. Today, biophysicists are discovering that this electrical layer is actually the primary canvas upon which biological architecture is drawn.

A Historical Coincidence in Morphogenesis & Bioelectricity (1952)

In 1952, within the same week, Alan Turing published his mathematical theory of morphogenesis via reaction-diffusion, and Hodgkin & Huxley published their biophysical model of bioelectric signaling.

Turing's model showed how unstirred chemical reaction and diffusion can break symmetry from a homogenous state, settling into patterns similar to leopard spots or tiger stripes, which informed how we think about morphological patterning in developmental biology. Hodgkin and Huxley proposed a biophysical model of bioelectrical signaling which was essentially a distributed version of Ohm's law.

Proving a Mathematical Equivalence (2016 - 2019)

Adam E. Cohen, a biophysicist at Harvard University who runs a lab that develops new tools to study biology, came to the realization that these two famously distinct models shared the same underlying mathematical structure. Each has a derivative for time, a non-linear reaction term, and a diffusion term. Because the math is the same, Cohen hypothesized that biology could use bioelectricity to draw stable morphological patterns, like Turing's tiger stripes, rather than just using it for transient signaling like brain waves.

To test this, they took blank HEK (Human Embryonic Kidney) cells and added sodium ion channels for excitability, potassium channels for a resting potential, a photosensitive channel rhodopsin actuator to optically trigger the cells, and a voltage indicator protein for imaging the cell's responses to stimuli using a high-speed camera.

They observed that as cells grew dense enough to couple with their neighbors via gap junctions, they began autonomously firing. There were regenerative waves that propagated through the culture, and in bigger cultures around 100,000 cells, multi-millimeter spiral patterns that led to periodic dynamics.

This proved the first half of Cohen's hypothesis by showing bioelectricity can act as a reaction-diffusion system. They still needed to look beyond moving signals to find stable patterns that connect to morphogenesis.

Spontaneous Pattern Formation via Bioelectricity (2020) 

To push this further, the Cohen Lab team created a quadrant to classify types of solutions by their variance in time or space:

• Uniform Space / Stable Time: Tissues at resting states.

• Uniform Space / Varying Time: Pacemakers (the whole tissue pulses together).

• Patterned Space / Varying Time: Action potentials and spiral waves.

• Patterned Space / Stable Time: The missing link of morphogenic patterns.

To prove the bioelectric mechanisms for resting patterns to spontaneously form in biology, the researchers looked at a homogeneous sheet of genetically identical cells. While conventional thinking assumed the tissue would remain electrically uniform, the emergent phenomenon was predicted to occur in gap junctions. These microscopic tunnels that allow neighboring cells to share ions and electrical voltage could provide the medium for the math to play out.

Because the cells are constantly pumping ions, they are an active, non-equilibrium system. The Cohen Lab discovered that when the electrical coupling between these cells reaches a specific threshold, the tissue undergoes a spontaneous phase transition. The electrical symmetry breaks and the uniform sheet segregates into distinct macroscopic regions. One region of the tissue suddenly locks into a highly polarized, high voltage state, while the adjacent region locks into a depolarized, low voltage state.

The most significant feature of this phenomenon is the border between these two regions: the Bioelectrical Domain Wall.

In physics, a domain wall is a topological boundary that separates distinct states of matter, like the boundary between north and south magnetic domains in a piece of iron. The Cohen Lab proved that biological tissues do the same thing with electricity, drawing a domain wall in the form of a localized constraint defined by a spontaneously-generated voltage cliff.

The domain wall is an emergent physical boundary. Without genetic code telling them to do so, the cells utilized the non-linear dynamics of their ion channels to draw a stark, macroscopic border across the tissue. This, in effect, was evidence of Turing's tiger stripes as resting bioelectric pattern that can drive morphogenesis.

Resilience of Topological Action Potentials in Biology (2023)

Inspired by condensed matter physics, where certain materials act as insulators in their bulk but as conductors at their boundaries, the lab investigated whether these boundary conditions would lead to the same emergent phenomenon in biology. This research would also challenge the fragility of classical biological excitability described by the standard Hodgkin-Huxley model, where a successful action potential firing requires a fine-tuned ratio of sodium channels to potassium channels.

The team engineered two different, bioelectrically non-excitable cell cultures and grew them in a dish, separated by a physical plastic barrier. If stimulated individually, neither would fire. Once the cultures grew dense, the barrier was removed to allow the two to touch and form a sharp boundary interface.

When the two bulks met, the cells at the boundary became highly excitable. They fired continuous topological action potentials that traveled exclusively along the boundary interface but never spilled into their respective bulks. To test the resilience of this activity, they subjected the boundary cells to parameter variations, skewing the sodium and potassium levels far beyond what a classical cell could survive. The boundary kept firing, meaning the topological physics allowed the interface to successfully propagate signals across a 1,000-fold variation in ion channel expression.

The Medium is the Message

If we zoom out, the Cohen Lab's research proves that biology does not need a top-down director or genomic blueprint to build a biological machine. By simply coupling cells together and letting them share ions, the tissue is driven out of electrical equilibrium. The mathematical inevitability of that non-equilibrium state forces the tissue to break symmetry and construct its own spatial map in the form of bioelectrical domain walls.

The implications extend beyond this particular project. In condensed matter physics, topological boundary waves are notoriously 'protected'. Cohen's research proved that biology utilizes this same topological physics to create highly robust, resilient signaling. The boundary physics provides a buffer against biological noise, ensuring critical signals survive even when the underlying cellular components fluctuate.

Not only are there implications for survival mechanisms, but evolutionary ones as well. Long before organisms had specialized neurons or brains, they had skin, guts, and other primitive tissues. If the boundaries between these tissues naturally acted as conductors due to topological physics, then early organisms possessed robust bioelectrical networks before the brain evolved. Neurons may simply be an evolutionary optimization of these boundaries.

This progression also connects to the statistical mechanics of condensed matter, where systems like the Antiferromagnetic Ising Model operate at scale through Markovian-style dynamics at local boundaries. There are also parallels to Nikta Fakhri's research in emergent self-organization through non-equilibrium thermodynamics. Physics, once again, does the heavy lifting- whether it is fluid mechanics building a living liquid crystal, or bioelectricity utilizing topological boundaries to form robust pre-neural networks.

As we look further into the frontier of biophysics, the next question emerges: once an organism uses the laws of physics to draw these bioelectrical maps, how does it use them to remember its own shape?