Biosensor physics: DNA folding in a crowded environment*

At the molecular level, biological systems operate in very crowded environments. It has long been recognized that crowding can affect the stability and phase transitions of the biopolymers comprising such systems. Similar issues arise in developing biotechnology applications based of dense arrays of surface-tethered polymers. In our recent work we directly measure the entropy reduction resulting from crowding/confinement using Wang-Landau computer simulation techniques [1]. Here we discuss the folding transition of a specific stem-loop forming, single-stranded DNA oligomer that has been studied extensively by the Plaxco group [2]. We develop a coarse-grained model for ssDNA (based on a flexible hard-sphere chain with square-well patch interactions that accounts for both H-bonding and base-pair stacking) and use it to examine the entropic effects associated with surface crowding. For the tethered ssDNA oligomer crowded by other tethered oligomers, we find, in agreement with experiment, that both stabilization and destabilization of the folded state are possible depending on the conformational state of the crowders. [1] Taylor, Macromolecules 50, 6967 (2017); J. Chem. Phys. 147, 166101 (2017); [2] Watkins et al, JACS 134, 2120 (2012); JACS 136, 8923 (2014).