Hydration Effects Turn a Highly Stretched Polymer from an Entropic into an Energetic Spring

Abstract

Polyethylene glycol (PEG) is a structurally simple and nontoxic water-soluble polymer that is widely used in medical and pharmaceutical applications as molecular linker and spacer. In such applications, PEG's elastic response against conformational deformations is key to its function. According to text-book knowledge, a polymer reacts to the stretching of its end-to-end separation by a decrease in entropy that is due to the reduction of available conformations, which is why polymers are commonly called entropic springs. By a combination of single-molecule force spectroscopy experiments with molecular dynamics simulations in explicit water, we show that entropic hydration effects almost exactly compensate the chain conformational entropy loss at high stretching. Our simulations reveal that this entropic compensation is due to the stretching-induced release of water molecules that in the relaxed state form double hydrogen bonds with PEG. As a consequence, the stretching response of PEG is predominantly of energetic, not of entropic, origin at high forces and caused by hydration effects, while PEG backbone deformations only play a minor role. These findings demonstrate the importance of hydration for the mechanics of macromolecules and constitute a case example that sheds light on the antagonistic interplay of conformational and hydration degrees of freedom.

Surface-induced effects in fluctuation-based measurements of single-polymer elasticity: A direct probe of the radius of gyration

“…Both PEG and HA form higher-order structures due to hydrogen bonding between neighboring monomers and/or between monomers and water. 9,14,23 High forces have been shown to disrupt these interactions, 9,14,24 which leads to deviations from WLC behavior, and can lead to elasticitybased estimates of l p that are smaller than l p in the absence of force. This issue is minimized here: those prior observations are based on AFM studies at a force scale of ≈100 pN.…”

“…Further, in the low-force regime, absolute extension becomes very small, leading to sensitivity to systematic errors based on, e.g., the precise tethering position of the polymer to the probe. 8,9 An alternate approach is based on the analysis of the fluctuations in polymer extension. 3,7 The fluctuation-based method is an application of linear response theory 10 and is discussed in detail elsewhere.…”

Single‐Molecule Force Spectroscopy Reveals Self‐Assembly Enhanced Surface Binding of Hydrophobins

“…[12] The force-extension curvesw ere well fitted by the worm-like chain (WLC) with ap ersistence length of about 0.4 nm and ac ontour length of approximately 40 nm ( Figure S7, Supporting Information), consistent with our calculation andp revious works on the PEG linker. [13] The observed single rupture peak (in contrast to multiple unfolding peaks) in the force-extension curvess uggest that HFBI remained folded before detaching from the surfaces. The high stability of HFBI due to the disulfide bridges supports this conclusion.…”

Exploring Rigid and Flexible Core Trivalent Sialosides for Influenza Virus Inhibition

“…Hence the OEG‐ spacer has to bridge a distance of approximately 2 nm. The length distribution of flexible OEG chains that we obtained from our previous MD simulations, suggested that the OEG‐linker must consist of at least 6–14 ethylene glycol units to span the distance between the ligand core and the binding sites (c.f. Supporting Information)…”