Emergence of highly-ordered hierarchical nanoscale aggregates on electrostatic binding of self-assembled multivalent (SAMul) cationic micelles with polyanionic heparin

Abstract

Article:Smith, David Kelham orcid.org/0000-0002-9881-2714 (2017) Emergence of highly-ordered hierarchical nanoscale aggregates on electrostatic binding of self-assembled multivalent (SAMul) N-di-(3-aminopropyl)-N-methylamine (DAPMA) head groups and aliphatic chains connected via an amide linkage, and investigate their ability to self-assemble and bind polyanionic heparin a process of potential clinical importance in coagulation control. Modifying the hydrophobic chain length tunes the self-assembly event, with C16-DAPMA having the lowest critical micelle concentration and also being the optimal heparin binder. Remarkably highly structured hierarchical nanoscale aggregates are formed on binding between the spherical cationic micelles and linear polyanionic heparin. C14-DAPMA and C16-DAPMA yield organized polycrystalline assemblies as observed by transmission electron microscopy (TEM), predicted in solution by mesoscale simulations and characterized by small-angle X-ray scattering (SAXS). This confirms that the micelles remain intact during the hierarchical assembly process and become packed in a face-centered cubic manner. The nanoscale assembly formed by C16-DAPMA showed the highest degree of order. Importantly, these studies indicate the impact of hydrophobic modification on self-assembly and heparin binding, demonstrate remarkably high stability of these self-assembled micelles even when forming strong electrostatic interactions with heparin, and provide structural insights into nanoscale hierarchical electrostatic assemblies.

Morphological control of self-assembled multivalent (SAMul) heparin binding in highly competitive media

“…This hierarchical assembly mechanism has been discussed in detail elsewhere for electrostatically-bound micelle-polyelectrolyte complexes. 19 TEM therefore supports the morphologies predicted by modelling and suggests they are not significantly disturbed by electrostatic binding to heparin.…”

Commercially Relevant Orthogonal Multi‐Component Supramolecular Hydrogels for Programmed Cell Growth

“…The CD intensity associated with DBS‐CONHNH 2 was also lower (Figure S2). TEM visualised both DBS‐CONHNH 2 nanofibres, and the semi‐crystalline nanostructures distinctive of complexes between C 16 ‐DAPMA and heparin (Figures B, S5 and S6) . However, in addition, it was also possible to identify some larger aligned structures (ca.…”

Self‐Assembled Multivalent (SAMul) Polyanion Binding—Impact of Hydrophobic Modifications in the Micellar Core on DNA and Heparin Binding at the Peripheral Cationic Ligands

“…[21] In terms of heparin binding,t he CE 50 was found to be 0.68 AE 0.09 and the EC 50 was 37 AE 5mm. [21] The heparin binding performance of C18-0 is therefore equivalentto, or better than, that of C18-1, continuing the trend in which those systemsw ith fewer alkenes are more effective heparin binders. However, given the differences in native self-assembledm orphologyb etween C18-0 and the other amphiphiles studied here, we decided not to extend the study of this system further.…”

“…Interestingly,w eh ave previously reported the synthesis of the fully saturated member of this familyo fa mphiphiles, which can be considered C18-0i nt he nomenclatureu sed here (previously namedC 18-DAPMA). [21] This fully saturated compound experienced some solubility problems and analysis of DLS by volume distribution indicated the formation of larger assemblies (93 AE 26 nm). [21] In terms of heparin binding,t he CE 50 was found to be 0.68 AE 0.09 and the EC 50 was 37 AE 5mm.…”

“…[21] This fully saturated compound experienced some solubility problems and analysis of DLS by volume distribution indicated the formation of larger assemblies (93 AE 26 nm). [21] In terms of heparin binding,t he CE 50 was found to be 0.68 AE 0.09 and the EC 50 was 37 AE 5mm. [21] The heparin binding performance of C18-0 is therefore equivalentto, or better than, that of C18-1, continuing the trend in which those systemsw ith fewer alkenes are more effective heparin binders.…”