Multiplateau Force–Extension Curves of Long Double-Stranded DNA Molecules

TL;DR

This paper shows that long DNA molecules with different segments can have multiple force plateaus when stretched, which might influence how cells process DNA.

Contribution

The study predicts multiple plateau regions in DNA force–extension curves based on segment composition and plateau force differences.

Findings

A composite DNA fragment with two segments shows two distinct plateau regions in its force–extension curve.

A three-segment DNA fragment exhibits three distinct plateau regions under stretching.

The extension during the first plateau is predominantly from one segment, such as poly(dA-dT) in a composite fragment.

Abstract

When highly stretched, double-stranded DNA exhibits a
plateau region
in its force–extension curve. Using a bead–spring coarse-grained
dynamic model based on a nonconvex potential, we predict that a long
double-stranded DNA fragment made of several consecutive segments
with substantially different plateau force values for each segment
will exhibit multiple distinct plateau regions in the force–extension
curve under physiologically relevant solvent conditions. For example,
a long composite double-stranded (ds) DNA fragment consisting of two
equal-length segments characterized by two different plateau force
values, such as the poly(dA-dT)-poly(dG-dC) fragment, is predicted
to exhibit two distinct plateau regions in its force–extension
curve; a long composite dsDNA fragment consisting of three segments
having three different plateau force values is predicted to have three
distinct plateau regions. The formation of mixed states of slightly
and highly stretched DNA, coexisting with macroscopically distinct
phases of uniformly stretched DNA is also predicted. When one of the
segments overstretches, the extensions of the segments can differ
drastically. For example, for the poly(dA-dT)-poly(dG-dC) composite
fragment, in the middle of the first plateau, 96.7% of the total extension
of the fragment (relative to Lx/L0 ≈ 1.0) comes from the
poly(dA-dT) segment, while only 3.3% of it comes from the poly(dG-dC)
segment. The order of the segments has little effect on the force–extension
curve or the distribution of conformational states. We speculate that
the distinct structural states of stretched double-stranded DNA may
have functional importance. For example, these states may modulate,
in a sequence-dependent manner, the rate of double-stranded DNA processing
by key cellular machines.

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