PMC:6723693 / 40469-43352
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/6723693","sourcedb":"PMC","sourceid":"6723693","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6723693","text":"We found the concept that small spherical micelles retain their shape while forming mesoscopic aggregate structure upon heparin binding quite intriguing. Accordingly, to investigate this aspect in more detail, we designed and optimized synthetically-simple, minimal self-assembling dendrons that could serve this purpose, ultimately ending up with “reduced versions” of C22G1, which is two molecules still featuring a single DAPMA polar head and a single apolar chain of 14 (C14G0) and 16 (C16G0) carbon atoms, respectively [24]. As per molecular design, in buffered solutions at physiologically ionic strength these two amphiphilic dendrons self-assembled into small, spherical nanostructures with high and positive ζ potentials (Dm = 5.8 ± 1.6 nm and ζ = + 41.3 ± 1.6 mV for C14G0 and 6.2 ± 1.3 nm and + 51.7 ± 2.2 mV for C16G0, respectively), and showed good heparin binding ability (CE50 = 0.88 and 0.46 for C14G0 and C16G0, respectively) yet inferior to those of C22G1, indicating that the structure this latter amphiphile was indeed optimized for binding the polyanion. However, given that both these simpler dendrons were endowed with the required characteristics (spherical micelle formation and heparin binding), we employed them to investigate the structure of the relevant heparin complexes starting from TEM imaging, as shown in Figure 8a,b for C16G0 as an example (analogue images were obtained for the alternative C14G0-based system). These TEM observations, beside confirming the spherical nature of these self-assembled dendrimers, suggest that their stability is preserved, without disruption or reorganization, upon heparin binding with which they form strong electrostatic interactions. However, since we were aware that TEM images were collected on dried samples, we wondered whether the drying process might have somewhat forced the systems (and, by extensions, also the other self-assembled dendrimers previously discussed) to assume such morphology. Therefore, we first resorted again to molecular simulations to predict the self-assembly and spatial organization of these two amphiphiles in the presence of heparin in solution. The output of these simulations (Figure 8c,d) shows that not only both molecules self-assemble in small, stable spherical micelles in the presence of the polyanion but, perhaps even more important, these are not randomly dispersed into the heparin solution but adopt a highly-ordered, hierarchical nanoscale structure matching a face-centered (fcc) organization, with lattice constant value a equal to 8.1 nm and 8.6 nm for the C14G0 and C16G0 self-assembled dendrimers, respectively. The corresponding center-to-center distance (a2) is equal to 5.7 nm in the case of the C14G0 micelles and to 6.1 nm for the self-assembled C16G0, in excellent agreement with the Dm values measured by DLS (5.8 and 6.2 nm, respectively, see above).","tracks":[]}