From the energetic standpoint, from the solid bars in Figure 13d we see that, when heparin binding is considered from the perspective of each single micellar monomer, the self-assembling dendron bearing the most flexible tail (i.e., C18,1G0) is endowed with the most favorable enthalpic term (∆H* = −24.02 kJ/mol) which, by overcompensating the unfavorable entropic contribution (T∆S* = −7.92 kJ/mol), ultimately leads to a quite favorable value of ∆G* (−16.10 kJ/mol). As the number of double bonds increases and, as reported above, Neff decreases, the relevant parameters of binding thermodynamics follow the same trend. Accordingly, for C18,2G0 ∆H* = −17.76 kJ/mol, T∆S* = −5.55 kJ/mol, and ∆G* = −12.21 kJ/mol, while for C18,3G0 ∆H* = −14.98 kJ/mol, T∆S* = −4.63 kJ/mol, and ∆G* = −10.35 kJ/mol, respectively. Of note, increasing the hydrocarbon chain stiffness brings about a small beneficial effect in entropic terms, as the molecules suffer less entropic penalties upon binding; yet, as at the same time, due to increased rigidity, the micelle monomers are less able to adapt their conformation for optimal electrostatic polyanion binding, and the enthalpic component is less effective in driving the intermolecular interactions. As a global result, the computational affinity ranking for the self-assembled dendrimers follows the same trend of their experimental counterpart, ie., C18,1G0 > C18,2G0 > C18,3G0. When the same analysis was applied from the viewpoint of heparin sugars, the variations of the three binding components (patterned bars in Figure 13d) paralleled those experienced by each micellar dendron. Accordingly, in binding the micelles generated by the most flexible dendron (C18,1G0) the polyanion can compensate a higher entropic penalty by gaining a substantially more favorable enthalpic contribution on its own, while it progressively adapts the enthalpy/entropy ratio on increasing micellar rigidity.