Melting of DNA in confined geometries

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ORIGINAL ARTICLE

Melting of DNA in confined geometries Arghya Maity1   · Navin Singh1 Received: 5 February 2020 / Revised: 10 June 2020 / Accepted: 3 September 2020 © European Biophysical Societies’ Association 2020

Abstract The stability of DNA molecules during viral or biotechnological encapsulation is a topic of active current research. We studied the thermal stability of double-stranded DNA molecules of different lengths in a confined space. Using a statistical model, we evaluate the melting profile of DNA molecules in two geometries: conical and cylindrical. Our results show that not only the confinement, but also the geometry of the confined space plays a prominent role in the stability and opening of the DNA duplex. We find that for more confined spaces, cylindrical confinement stabilizes the DNA, but for less confined spaces conical geometry stabilizes the DNA overall. We also analyse the interaction between DNA sequence and stability, and the evenness with which strand separation occurs. Cylindrical and conical geometries enable a better controlled tuning of the stability of DNA encapsulation and the efficiency of its eventual release, compared to spherical or quasi-spherical geometries. Keywords  DNA · Melting temperature · Encapsulation

Introduction The most abundant conformation of deoxyribonucleic acid (DNA) is a double-helical structure (also known as the Watson–Crick double helix). The genetic information for entire organisms is coded in a sequence composed of four nucleotides: adenine (A), guanine (G), cytosine (C), thymine (T) (Watson and Crick 1953). On increasing the temperature of a solution containing dsDNA, the double-stranded conformation changes to a single-stranded conformation. This process is known as DNA melting or denaturation (Zhang et al. 1997; Williams 2016; Vologodskii and Frank-Kamenetskii 2018; Frank-Kamenetskii and Prakash 2014; Poland and Scheraga 1966; Fisher 1984; Richard and Guttmann 2004). Other methods by which DNA can be melted include changing the pH of the solution and physically pulling on either of the strands (Sadhukhan and Bhattacharjee 2014; Hatch et al. 2008; Kumar and Li 2010). The importance of understanding the conformational and mechanical characteristics of this molecule lies in its wide application in molecular motors, * Arghya Maity [email protected] Navin Singh [email protected]‑pilani.ac.in 1



Department of Physics, Birla Institute of Technology and Science, Pilani, Rajasthan 333 031, India

DNA computers, DNA origami, on DNA chips, and in biomedicine, etc. To perform gene therapy (Jour Putnam 2006), nanorobotics (Yurke et al. 2000) and diagnostics (Dharmadi and Gonzalez 2004), DNA degradation is a major obstacle for its effective and efficient use. DNA degradation eventuates in chemical breakdown (Jour Putnam 2006) or sometimes through mechanical forces (Murphy et al. 2006). In gene therapy techniques, DNA is protected by a physical barrier. Many strategies have been used to get better results while delivering or applying DNA-like complex