Probing Persistence in DNA Curvature Properties with Atomic Force Microscopy

We elaborate on a mean-field extension of the wormlike chain model that accounts for the presence of long-range correlations (LRC) in the intrinsic curvature disorder of genomic DNA, the stronger the LRC, the smaller the persistence length. The comparison of atomic force microscopy imaging of straight, uncorrelated virus and correlated human DNA fragments with DNA simulations confirms that the observed decrease in persistence length for human DNA more likely results from a sequence-induced large-scale intrinsic curvature than from some increased flexibility.

Figure 1

Persistence length $l_p(L)=⟨R^2⟩/2L$ computed with Eq. (4) for $2A_d=540\mathrm{bp}$: (a) ${\sigma }_0=0.01$, $H=0.5$, 0.6, 0.7, 0.8 from top to bottom; (b) $H=0.8$ and ${\sigma }_0=0.001$, 0.008, 0.02, 0.04 from top to bottom. The black dots correspond to DNA simulations with ${\sigma }_0=0.008$ and $H=0.8$, when averaging over $N={10}^3$ different frozen chains.

Figure 2

AFM images of $L=800\mathrm{bp}$ intrinsically straight (a) and $L=2200\mathrm{bp}$ HCV (b) and human (c) DNA molecules. DNA simulations of $N=100$ $L=2200\mathrm{bp}$ chains: 2D frozen chains with uncorrelated ($H=1/2$, dark red) and LRC ($H=0.8$, light green) curvature angle fluctuations of amplitude ${\sigma }_0=0.008$ (a′); 2D equilibrium conformations (black) generated with $2A_d=540\mathrm{bp}$ from a frozen chain with uncorrelated ($H=1/2$, ${\sigma }_0=0.02$, red) (b′) and with LRC ($H=0.8$, ${\sigma }_0=0.008$, green) (c′).

Figure 3

Internal end-to-end distance measurement of $l_p(s)$ vs $s$ when averaging over $N$ samples of length $L=2200\mathrm{bp}$ when nonspecified. (a) AFM imaging: (▵) intrinsically straight DNA ($N=131$, $L=800\mathrm{bp}$), (□) HCV DNA ($N=61$), (○) human chromosome 21 DNA ($N=91$), (⋄) human chromosome 8 DNA ($N=81$). The WLC model predictions [Eq. (3)] are in solid ($l_p=540\mathrm{bp}$), dashed ($l_p=485\mathrm{bp}$) and dotted ($l_p=385\mathrm{bp}$) lines. (b) DNA simulations of $N=100$ 2D equilibrium conformations generated with $2A_d=540\mathrm{bp}$ from a frozen chain that is: (▴) straight, (▪) with uncorrelated ($H=1/2$, ${\sigma }_0=0.02$) curvature disorder [Fig. 2bx2032], (●) with a LRC ($H=0.8$, ${\sigma }_0=0.008$) curvature disorder [Fig. 2cx2032], (◆) with another frozen LRC chain. The solid and dashed lines are the same as in (a).