Cover Image and Art: Maia Lazor
Imagine a bustling city with sprawling infrastructure and busy constituents. In any high-functioning environment, communication is key to running things smoothly. Across human cities, or on a macroscopic scale, electricity facilitates the mass transfer of information, powers communication, and maintains order. Just as electricity runs our world, it is also critical for life on a microscopic scale, permeating biological systems in both familiar and unexpected ways. Electrical signaling between neurons may be the most intuitive example of electricity shaping life, but it is far from the only one; mycobacterium tuberculosis attacking a lung, a predatory venus flytrap closing its trap, a heart pumping blood through a body—these distinct biological events all rely on electrical signaling to different degrees. If one looks closer and a little further back in evolutionary history, it becomes apparent that bioelectrical signals permeate all forms of life in patterns that mirror over time.
Bacterial Biofilms: Ancient or Advanced?
Despite their relatively simplistic biology, basic bacterial systems have been found to share functional links with the most advanced biological systems yet to have evolved. For example, bacterial cells contain genes that are homologous, or functionally similar, to eukaryotic genes that code for neuron-specific features, such as voltage-gated ion channels and synaptic proteins. In fact, one hypothesis suggests that voltage-gated channels first evolved from ancient prokaryotes’ need for water and ion regulation.1 In our bodies, voltage-gated sodium and potassium channels rapidly open and close in response to fluctuations in a neuron’s membrane potential, or electric charge difference, generating an electric signal known as the action potential—one of the most complex forms of biological communication. This organization is incredibly useful for transmitting signals across long distances, whether in multicellular organisms or in communities of smaller organisms like bacteria. While bacteria are often thought of as solitary, free-floating organisms, they lead social lives out in nature, often forming into biofilms, or “cities” of their own.
A biofilm is a densely packed community of bacteria with enhanced functions and protections for individual cells and growing colonies.2 Much like an urban landscape, a biofilm is a diverse population of cells, all with different roles and metabolic states that work together to support its growth and adaptability. Biofilms form in nutrient-limited environments when a foundational group of bacterial cells attaches itself to a moist surface using built-in hair-like appendages known as pili and fimbriae. These foundational cells then multiply to form microcolonies, which are similar to what you might observe on a petri dish. Simultaneously, the growing biofilm secretes an extracellular matrix, like a bacterial glue containing a wide variety of proteins and other biomolecules. This slimy substance shields the internal microcolonies from the environment and forms a three-dimensional system that maintains the flow of nutrients and waste. The extracellular matrix is also believed to support the heightened antibiotic resistance of biofilms by providing a physical barrier that blocks and neutralizes antibiotics. Once the numerous microcolonies mature, they detach from the biofilm as motile, or independent, cells to initiate biofilm formation on new surfaces.3
Various estimates show that anywhere from 40-80% of bacterial species naturally aggregate into biofilms because of the significant survival advantages afforded by the extracellular matrix.4 You may be more familiar with bacterial colonies grown on petri dishes, but in fact, only around 1% of all bacterial species are culturable, meaning that they aggregate into observable colonies under laboratory settings. A biofilm exhibits many collective mechanisms, such as quorum sensing for coordinated gene expression and cell differentiation; this complexity likens it to a multicellular organism. Yet, biological education and research practice traditionally view the functional unit of bacteria as the cell, not the biofilm. Recognizing bacteria as communal organisms, rather than isolated cells, opens the door to new ways of researching their behavior, communication, and pathogenicity. One lab pioneering this focal shift is the Gurol Suel Lab at UC San Diego, which has spent the last decade investigating electrical signaling and emergent behaviors in biofilms. In their groundbreaking 2015 publication, “Ion channels enable electrical communication in bacterial communities,” the Suel Lab provided the first evidence that bioelectrical signaling is not exclusive to excitable cells like neurons or muscles. Rather, bacterial biofilms undergo a phenomenon of synchronized oscillations in their metabolic rates to proliferate and defend themselves. This is accomplished through a mechanism of ion-channel-mediated-signaling that bears striking similarities to neuronal communication in animals.
Our Shared Sparks of Life
In our brains, neurons are the electric highways of life, rapidly firing signals that coordinate our thoughts, words, and actions. When traffic is light, the inside of a neuron is negatively charged compared to the outside. But when an electric signal is received, voltage-gated channels open, allowing sodium ions to rush in and make the inside of the neuron more positive. This sudden depolarization, or positive shift in voltage, travels down the neuron like a wave, passing the signal to the next neuron or a target cell. In the wake of the action potential, potassium channels open to restore the negative charge inside the cell and prepare for the next stimulus.5 Similarly, biofilm cells utilize ion channels to propagate their own signals for survival. However, unlike neuronal signals, which are highly precise and carry specific information from one neuron to the next, biofilm electrical signaling is a broader, population-wide phenomenon. Under metabolic stress, specifically a lack of glutamate, YugO channels on the membranes of interior bacterial cells will open to release potassium ions. These channels function similarly to neuronal potassium channels and cause the cell to depolarize. This produces a positive change in the local extracellular current, triggering nearby cells to also depolarize until the signal reaches the biofilm’s periphery (Figure 1).6 Both systems are elegant examples of electricity on a biological microscale, but how does bioelectrical signaling benefit biofilms?
Think of a biofilm as a bacterial “city” in which an electric grid dictates everything from resource allocation (who gets nutrients) to construction plans (which areas should grow or shrink). Just as a city’s grid has the ability to reroute electricity to maintain overall function, a biofilm utilizes electrical signaling to modulate the growth rates of different regions in response to metabolic stress. In particular, cells on the periphery of Bacillus subtilis biofilms will periodically stop growing to prevent the starvation of interior cells. The fluctuation in metabolic rates is the result of a limited supply of glutamine, an amino acid and essential bacterial nutrient that is manufactured from the charged metabolites glutamate and ammonium. Interior cells contain enzymes that regularly produce ammonium, which eventually diffuses to cells on the biofilm’s periphery. However, glutamate can only be sourced from the environment, giving peripheral cells easier access to glutamate and a metabolic advantage. To redistribute the available nutrients, peripheral cells halt their growth to allow glutamate to diffuse to the interior cells (Figure 2). Interior cells can then produce ammonium from a new supply of glutamate and begin the cycle anew.7 In contrast to a neuron encoding distinct messages using ion flow, a biofilm adjusts its “power grid” to balance energy demands across regions and fortify its structure.
In a proof-of-concept study to support this decade of findings, the Suel Lab combined forces with the Rolandi Research Group from UC Santa Cruz who specialize in bioelectronic systems and devices. Together, the researchers successfully integrated Bacillus subtilis biofilms with bioelectronic ion pumps that deliver potassium ions regionally within the biofilm. In their previous studies of biofilm oscillations, the Suel Lab used a microfluidic device, often described as a “lab on a chip,” for precise fluid measurements and ion delivery. A biofilm sat inside a chamber with two openings where an ionic solution flowed in then out, eliciting whole-biofilm growth and oscillations. This device, however, did not allow for spatiotemporal control over biofilm growth. Since the chamber delivered ions to the entire biofilm, there was no way to tell how separate biofilm regions would respond to ion delivery. In contrast to the microfluidic chamber, the bioelectronic ion pump, consisting of four glass capillary tubes lined with a hydrogel, facilitated ion delivery to specific spots on the biofilm. Once potassium ions were delivered into the extracellular fluid, YugO channels would open to depolarize the cells in that region. This promoted biofilm growth in an anisotropic, or non-uniform, manner, while the “control” biofilm, without the added device, experienced isotropic, or uniform, growth. Through this research, the Suel Lab realized that control over the electrical dynamics of bacterial cells would allow for the manipulation of bacterial biofilm morphology.8
Frying the Lines
Maintaining a balance of metabolic rates is shown to maximize biofilm robustness against external attacks. Because of their low metabolic rates and nested position within the biofilm, interior cells are well-equipped to resist antibiotics and guarantee the biofilm’s long-term survival. Severing the communication lines between the interior and periphery would therefore prevent the biofilm’s meticulous metabolic cycle, sabotaging its normal growth and function. Bacterial infections involving biofilms, such as cystic fibrosis and chronic wound infections, are notoriously difficult to treat due to a biofilm’s ability to shield bacteria from both the immune system and antibiotics. Based on the Suel Lab’s past research, a new, drug-free method of treatment that exploits bacterial excitability could be effective in treating harmful biofilms. Let’s return to the neuron’s action potential: to transmit one signal after the other, a neuron must rapidly depolarize and hyperpolarize, or shift to a negative voltage. In between transmissions, there is a mandatory refractory, or recovery, period before the neuron can re-enter an excitable state. Bioelectronic Localized Antimicrobial Stimulation Therapy (BLAST), a device created by the Suel Lab, leverages this concept in Staphylococcus epidermidis, a common skin bacteria that forms into a biofilm when it infects skin or contaminates medical devices. In its virulent state, S. epidermidis—a leading cause of hospital infections—forms antibiotic-resistant biofilms on implants, making it a critical target for treatment. First, exposure to an acidic pH of 5, typical of healthy skin, excites the biofilm and makes it responsive to external electric stimuli. Then, BLAST taps into S. epidermidis’ “electric grid” and delivers weak 1.5 volt signals to the bacteria, inducing a kind of refractory period. During this period of hyperpolarization, signals cannot be transmitted, preventing the coordination of metabolic rates between the interior and periphery. When tested on pig skin inoculated with S. epidermidis, BLAST decreased biofilm size by tenfold after an 18-hour treatment cycle and decreased the expression of antibiotic resistance genes. As antibiotic resistance continues to threaten public health, innovations like BLAST offer a promising, drug-free strategy to outsmart biofilms and protect against bacterial infections.9
The Concluding Transmission
From neurons firing in our brains to bacterial biofilms coordinating survival, bioelectrical signaling serves as the power grid that fuels life across biological domains. What was once thought to be exclusive to excitable cells has now been uncovered as a key mechanism driving the endurance of bacterial communities, further revealing strong functional links between microbes and complex life. The Suel Lab’s discoveries of metabolic coordination and ion-channel-mediated signaling have not only expanded our understanding of biofilm communication but have also paved the way for innovative bioelectronic therapies like BLAST. By recognizing the similarities between the communication systems of vastly different domains of life, we can gain new biological perspectives and apply this knowledge to solving problems in medicine, biotechnology, and beyond. Biofilms will continue to evolve, but so will our innovations to disrupt or tap into their power.
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- Muhammad MH. 2020. Beyond risk: Bacterial biofilms and their regulating approaches. Frontiers. [accessed 2024 Dec 12]; https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00928/full
- Penesyan A. 2021.Three faces of biofilms: A microbial lifestyle, a nascent multicellular organism, and an incubator for Diversity. Nature News. [accessed 2024 Dec 12]; https://www.nature.com/articles/s41522-021-00251-2
- Flemming H-C, Wuertz S. 2019. Bacteria and archaea on Earth and their abundance in biofilms. Nature Reviews Microbiology. [accessed 2024 Dec 12]; https://www.nature.com/articles/s41579-019-0158-9.
- Grider M. 2023. Physiology, Action Potential. National Institutes of Health. [accessed 2025 February 22]; https://www.ncbi.nlm.nih.gov/books/NBK538143/
- Prindle A. 2015. Ion channels enable electrical communication in bacterial communities. Nature. [accessed 2024 Dec 12]; https://www.nature.com/articles/nature1570
- Liu J. 2015. Metabolic co-dependence gives rise to collective oscillations within biofilms. Nature. [accessed 2024 Dec 12]; https://www.nature.com/articles/nature14660
- Prinzi A, Rohde R. 2023. The role of bacterial biofilms in antimicrobial resistance. ASM.org. [accessed 2024 Dec 12]; https://asm.org/articles/2023/march/the-role-of-bacterial-biofilms-in-antimicrobial-re
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