Control of DNA denaturation bubble nucleation to advance nano-biosensing

In the demanding biosensing environment, improving selection efficiency strategies has become an issue of great significance. DNA minicircles containing between 200 and 400 base-pairs, also named microDNA, are representative of the supercoiled DNA loops found in nature. Their short size makes them extremely susceptible to writhe and twist, which is known to play a central role in DNA denaturation. We investigate minicircle lengths and superhelical densities that induce DNA denaturation bubbles of nanometer size and control well-defined long-life. Mesoscopic modeling and accelerated dynamics simulations allow us to study accurately the thermodynamic and dynamical properties associated with the nucleation and closure mechanisms of long-lived denaturation bubbles. Our results pave the way for new types of DNA biosensors with enhanced selectivity for specific DNA binding proteins.