Multi-plateau force-extension curves of long double-stranded DNA

Abstract

AbstractWhen highly stretched, double-stranded DNA exhibits a plateau region in its force- extension curve. Here, we investigate the possibility of multiple distinct plateau regions in the force-extension curves of non-supercoiled double-stranded DNA under physio- logically relevant conditions, and explore how their existence and properties are related to the DNA sequence. Using a bead-spring coarse-grained dynamic model based on a non-convex potential, we predict that a long non-supercoiled double-stranded DNA fragment made up of several segments with substantially different plateau force values for each individual segment will exhibit multiple distinct plateau regions in the force- extension curve under physiological solvent conditions at room temperature. The order of the segments does not affect the force-extension curve or the distribution of confor- mational states. As an example, a double-stranded DNA fragment consisting of two equal-length segments with two different plateau force values (poly(dA-dT)-poly(dG- dC) fragment) is predicted to exhibit two distinct plateau regions in its force-extension curve; a fragment consisting of three almost equal-length segments having three dif- ferent plateau force values (poly(dA-dT)-torsionally constrained DNA-poly(dG-dC) fragment) is predicted to have three distinct plateau regions. The formation of mixed states of slightly and highly stretched DNA, co-existing with macroscopically distinct phases in several segments in the plateau regions, is also predicted. We speculate that the distinct structural states of stretched double-stranded DNA may have functional importance. For example, these can modulate, in a sequence-dependent manner, the rate of double-stranded DNA processing by key cellular machines.