Sliding Contact Dynamic Force Spectroscopy Method for Interrogating Slowly Forming Polymer Cross-Links

Abstract

10

Polymer sequencing by molecular machines: a framework for predicting the resolving power of a sliding contact force spectroscopy sequencing method

“…Analysing sliding contact force spectra In addition to previously published 8,9 datasets using α-CD and stations 1, 2, 4 and 5 on PEG axles ( pyromellitic acid, aminoaniline, guluronic and mannuronic acid respectively; see Fig. 2 for structures), we have conducted SCFS experiments using β-CD beads in order to probe the effect of differences in pore size.…”

“…We have recently published evidence that consecutive stations can be distinguished in space from each other. 9 Examples where this new approach may yield new information include the study of micro-and macroheterogeneity in protein glycosylation 41 and the pattern of monosaccharide decoration in polysaccharides, including hemicelluloses whose structure helps determine plant cell wall recalcitrance in bioenergy applications. 42,43 In both cases, the current state of the art method of analysis is mass spectrometry (MS).…”

“…Recently, the emergence of sequence-defined synthetic polymers has created a new class of materials in which relevant properties may be controlled with much greater precision than before, where sequence directly controls function. [5][6][7] Previously the authors 8,9 and others 10 explored the feasibility of a new route, here called sliding contact force spectroscopy (SCFS), to obtaining sequence information in linear heteropolymers by atomic force microscopy (AFM), but the limits and applicability of the method have not been fully explored. Here we set out to describe the parameters that determine how easy or difficult it is to pass a cyclodextrin (CD)-based macrocycle over a particular monomer, and from that basis derive a framework within which we can predict whether the monomers in a particular copolymer are distinguishable using this method.…”

“…18 The most common terminology 19 for describing the processes occurring in a rotaxane depicts a macrocyclic 'bead' shuttling between 'stations' on the polymer axle. In the SCFS method described here and previously, [8][9][10] the bead is α-or β-cyclodextrin (α-CD and β-CD hereafter) and the stations are the individual monomers comprising the polymer axle, while the AFM probe supplies the unidirectional driving force for shuttling the bead between stations (hereafter 'sliding') under a load generated by the controlled separation of probe and sample. Fig.…”

“…22,23 We have shown previously that measurements made with the SCFS approach described here yielded excellent agreement with the predicted positions of aromatic rings substituted into PEG polymers based upon the measured molecular weights of the polymers, 8 and that the CD bead could be used to unzip interactions between the polymer axle and molecules bound to specific sequences within that polymer. 9 Thus the available evidence suggests that SCFS may offer a method for mapping or sequencing long, linear polymers where there are large differences between monomers or blocks, or where specific sequences are recognised by other molecules. However, the limits on the size and nature of the different monomer stations and macrocyclic beads for which differences in force may be distinguished remain undefined.…”