We investigate, by means of computer simulations, the formation of soft nanoparticles by irreversible intramolecular cross-linking of homofunctional polymer precursors in good solvent. Simulations reveal that the early and intermediate stages of the cross-linking process are dominated by bonding at short contour distances. Because of the initial selfavoiding character of the precursor, bonding at long contour distances, which is the efficient mechanism for global compactation, is a rare event that essentially occurs in the late stage of cross-linking. Thus, irreversible cross-linking of precursors with identical molecular weight and linker fraction produces both compact and sparse objects. This is confirmed by a detailed analysis of the size and shape distribution of the fully cross-linked nanoparticles. We also investigate intramolecular cross-linking of heterofunctional polymers with two species of orthogonal linkers, bonding between distinct species being forbidden. It is found that simultaneous cross-linking of both species and sequential cross-linking (activation of one species after full cross-linking of the other) lead to the same structural properties for the resulting nanoparticles. The heterofunctional nanoparticles are on average smaller and more spherical than the homofunctional counterparts, though still a significant fraction of sparse objects is found. The simulation results are compared with results from SEC/MALLS and SAXS experiments in real polymeric nanoparticles.

Single-chain nanoparticles (SCNPs) are unimolecular soft nano-objects, consisting of individual polymer chains collapsed to a certain degree by means of intramolecular bonding. Many of the potential applications of SCNPs rely on their particular molecular architecture. Even if the ultimate goal is to produce globular protein-like soft nanoparticles, recent SANS and SAXS results -supported by computer simulations-indicate that SCNPs in solution actually adopt sparse configurations. Herein we compile size data from the literature for a large number of SCNPs in solution, covering from covalent to non-covalent bonded SCNPs, and provide a comparison with the corresponding data for compact or partially swollen globules of the same nature and molar mass. This comparison gives a clear idea of how far from the compact globule limit are current SCNPs. A quantification of the departure from the globular state is provided in terms of size scaling laws. This procedure facilitates a comparison with the size scaling laws observed for folded proteins with globular conformation as well as intrinsically disordered proteins which, on average, exhibit a certain local compaction when compared to chemically denatured proteins. Lastly, the underlying physical mechanism for the noncompact morphology of SCNPs in solution is put forward and guidelines for the potential synthesis of true SCNP globules in solution are suggested.

By means of large-scale computer simulations and small-angle neutron scattering (SANS), we investigate solutions of single-chain nanoparticles (SCNPs), covering the whole concentration range from infinite dilution to melt density. The analysis of the conformational properties of the SCNPs reveals that these synthetic nano-objects share basic ingredients with intrinsically disordered proteins (IDPs), as topological polydispersity, generally sparse conformations, and locally compact domains. We investigate the role of the architecture of the SCNPs in their collapse behavior under macromolecular crowding. Unlike in the case of linear macromolecules, which experience the usual transition from self-avoiding to Gaussian random-walk conformations, crowding leads to collapsed conformations of SCNPs resembling those of crumpled globules. This behavior is already found at volume fractions (about 30%) that are characteristic of crowding in cellular environments. The simulation results are confirmed by the SANS experiments. Our results for SCNPs--a model system free of specific interactions--propose a general scenario for the effect of steric crowding on IDPs: collapse from sparse conformations at high dilution to crumpled globular conformations in cell environments.

No abstract