ITC-Derived Per-Contact Kd Fed into Bell-Model 2D Membrane Adhesion Kinetics Predicts Minimum OmpC Density for T4 Productive Adsorption

Phage therapy is a promising alternative to antibiotics: instead of drugs, you use bacteriophages — viruses that naturally hunt and kill bacteria — to treat infections. The catch is that these viruses are picky. A phage like T4 has to physically grab onto specific proteins on the surface of a bacterium (in this case, a protein called OmpC on E. coli) before it can inject its genetic material and start killing. If there aren't enough of those receptor proteins on the bacterial surface, the phage just bounces off and nothing happens. But exactly how many receptors are 'enough' has been largely a matter of guesswork. This hypothesis proposes borrowing a set of equations originally developed in the 1970s to describe how cells stick to surfaces — called the Bell model — and combining it with precise lab measurements to predict that critical receptor density. The idea is to measure how tightly T4's 'grabbing arm' (a protein called gp37) binds to OmpC using a technique called isothermal titration calorimetry, which works like a tiny thermometer that detects the heat released when two molecules lock together. Then, combine that binding strength with how fast OmpC proteins drift around on the bacterial membrane (measured separately), and run it all through the Bell model math. The result should be a formula that predicts: below X receptors per square micron of bacterial surface, infection fails; above it, it succeeds — not as a sharp cliff, but as a smooth S-shaped curve. What makes this interesting is the cooperative twist: T4 doesn't just need one contact point, it needs at least three of its six 'leg-like' tail fibers to grab receptors simultaneously to trigger an irreversible change that commits the virus to infecting. That cooperative requirement makes the math richer and the prediction more biologically realistic than simple lock-and-key models.

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