Biofilm life in layers
Grow a microbial city one cell at a time. Food and medicine diffuse through 57,600 habitats; microbes spend energy, build matrix, divide, inherit traits and mutate. The picture is beautiful, but the lesson is precise: organisms sharing one colony can inhabit profoundly different worlds.
The same colony contains different lives
A biofilm is not merely a heap of identical bacteria. Molecules arrive by flow and spread by diffusion; cells near an exposed frontier consume them first. That creates gradients. A fast-growing surface cell and its genetically identical relative deep in the film can therefore have very different metabolisms, risks and futures. This lab makes that hidden geography visible.
Molecules spread
Food and antibiotic diffuse locally. Flow refreshes exposed liquid; consumption makes the gradient.
Energy decides
Cells pay for maintenance and inherited traits. Enough food funds division; starvation slows metabolism.
Builders reshape the niche
Costly extracellular matrix remains after cells die, anchoring neighbours against flow without becoming magic armour.
Offspring vary
Daughters inherit metabolism, resistance and adhesion. Rare copying changes let selection act on variation already present.
Surviving is not always resistance
Resistance is inherited. A resistant cell can keep growing at a drug level that arrests a susceptible cell, but its defence carries an energy cost here.
Tolerance is physiological. A quiet, food-limited cell may be killed more slowly by this growth-dependent drug even with a susceptible genome. When food returns, its descendants remain susceptible.
Four experiments, four questions
- Where does treatment fail? Open Hidden survivors, use the Metabolism lens, then pulse. The active frontier collapses first while much of the quiet interior outlasts it. Washout eventually lets susceptible survivors regrow.
- What does selection actually do? In Resistance race, resistant founders begin slower. Pulse once and watch their share rise; leave the culture drug-free and the growth cost can reverse that advantage.
- Who pays for a shared shelter? In Builders and hitchhikers, use the Matrix lens. Green-gold builders pay to anchor a neighbourhood; faster non-builders can occupy the shelter. Increase flow to expose the trade-off.
- Does evolution have a destination? Run Adaptive radiation, change food and flow, and compare the Genome lens before and after. Different environments favour different compromises; there is no universally best microbe.
What the model means — and what it does not
Biofilm is a qualitative hybrid model: a local reaction–diffusion grid coupled to individual digital microbes. It is not a clinical treatment calculator, does not represent a particular species, and intentionally models one abstract growth-dependent antibiotic rather than claiming that every drug behaves alike. One pixel is a habitat, not a literal bacterium drawn to scale.
The core lessons are evidence-based. In a Pseudomonas aeruginosa biofilm system, Walters and colleagues found oxygen limitation and low metabolic activity correlated with antibiotic tolerance more strongly than poor drug penetration. The field's consensus definitions distinguish inherited resistance from slower killing without increased MIC, while experiments on fluid channels in Bacillus subtilis biofilms show that real colonies can transport resources in ways this deliberately small rule set leaves out. The omissions are part of the lesson: useful models explain a mechanism; they do not become the organism.