Since the assays previously employed to monitor aggregation and heparin binding of the selected C22G1 amphiphilic dendron (Figure 3a) were carried out either in pure water or at very low salt concentration (≤5 mM) [36], in the first place we decided to investigate in detail the behavior of this molecule in more biologically relevant media. To the purpose, we initially gained information of the generation of G22G1 self-assembled nanostructures under different ionic strengths using computer-assisted multiscale molecular simulations [21]. In particular, exploiting a combination of atomistic and mesoscale modeling we predicted that at the physiological salt concentration (150 mM NaCl), C22G1 self-organizes into well-defined spherical micelles characterized by an aggregation number (Nagg) of 24 ± 1, a total surface charge (Ntot) of +96 ± 4, and an average micellar diameter (Dm) of 9.3 ± 0.1 nm (Figure 3b). Contextually, when C22G1 was challenged in silico for self-assembling under no-salt conditions, simulations still anticipated the formation of spherical nano-objects, yet with substantially smaller Nagg (11 ± 3), Ntot (44 ± 12), and Dm (6.3 ± 0.5 nm) (Figure 3c). The predicted increase of the micellar aggregates in response to increasing ionic strength was attributed to the salt-mediated screening of the micellar surface charge paralleled by the increasing contribution of the hydrophobic interactions. These two effects, acting in synergy, allow a larger number of individual dendrons to be incorporated into the nanomicelles, ultimately leading to larger nanoassemblies. Interestingly, at variance with the covalent G2 PAMAM molecule discussed above, the non-covalent nature of the G22G1 nanostructures endows them with the ability to respond to this physiologically-relevant environmental stimulus by modifying their characteristic dimensions to an extent covalent would be unable to reach.