Mechanical properties of DNA-like polymers

Abstract

The molecular structure of the DNA double helix has been known for 60 years, but we remain surprisingly ignorant of the balance of forces that determine its mechanical properties. The DNA double helix is among the stiffest of all biopolymers, but neither theory nor experiment has provided a coherent understanding of the relative roles of attractive base stacking forces and repulsive electrostatic forces creating this stiffness. To gain insight, we have created a family of double-helical DNA-like polymers where one of the four normal bases is replaced with various cationic, anionic or neutral analogs. We apply DNA ligase-catalyzed cyclization kinetics experiments to measure the bending and twisting flexibilities of these polymers under low salt conditions. Interestingly, we show that these modifications alter DNA bending stiffness by only 20%, but have much stronger (5-fold) effects on twist flexibility. We suggest that rather than modifying DNA stiffness through a mechanism easily interpretable as electrostatic, the more dominant effect of neutral and charged base modifications is their ability to drive transitions to helical conformations different from canonical B-form DNA.

The free solution mobility of DNA and other analytes varies as the logarithm of the fractional negative charge

“…The acronyms used to designate the various thymine‐modified DNAs are indicated in the figure; the acronyms and chemical sequences of the R substituents are given in first two columns of Table . The preparation of the thymine‐modified DNAs and their characterization are described elsewhere .…”

Nanostructures from Synthetic Genetic Polymers

“…However, the comparatively low biostability and immunogenicity of natural nucleic acids, together with limited chemical diversity and constraints on architecture and self‐assembly dynamics, restrict the scope of potential applications of DNA and RNA nanotechnology. Although some improvements might be gained though novel design strategies or sporadic incorporation of DNA modifications, we reasoned that a broad expansion of the range of nucleic acid chemistries available for nanotechnology could allow designs to exploit physicochemical properties beyond those of natural polymers.…”

“…[12] Such programmable, self-assembling DNA and RNA nanostructures have shown potentialf or aw ide variety of applications, [13] including sensing, [14] in vivoc omputation, [15] siRNA delivery, [16,17] encapsulation and releaseo ft herapeutic cargo, [18][19][20] organisation of biosynthetic enzymes on supramolecular assemblies, [21,22] or even formation of membrane-spanning pores. [23] However,t he comparatively low biostability [24] and immunogenicity [25] of natural nucleic acids, together with limited chemical diversity and constraints on architecture and self-assembly dynamics, [26] restrictt he scope of potentiala pplicationso fD NA and RNA nanotechnology.A lthoughs ome improvements might be gained thoughn ovel designs trategies [29] or sporadic incorporation of DNA modifications, [30][31][32] we reasoned that ab road expansion of the range of nucleic acid chemistries availablef or nanotechnology could allow designs to exploit physicochemical properties beyond those of natural polymers.Here, we report the construction of nanotechnology objects with wholesale replacement of natural nucleic acid strands with unnatural analogues,s pecifically synthetic geneticp olymers, also known as xeno nucleic acids (XNAs). XNAs have previously been shown to be capable of XNA-XNA duplex formation [33,34] and can fold into 3D structures,f orming ligands (aptamers) [28,35,36] and catalysts (XNAzymes).…”

Stretching Wormlike Chains in Narrow Tubes of Arbitrary Cross-Sections

“…The statistical behaviors of semiflexible polymers confined in nano-and micro-tubes are fundamental problems in polymer physics and have been investigated both experimentally and theoretically for decades [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. A thorough understanding of these problems is very important in the development of various application techniques that exploit the effects of confinement and stretching on polymers, including genome mapping [15,16], DNA sorting [17], and DNA denaturation mapping [18,19], etc.…”