RESUMEN
Understanding self-assembly in confined spaces is essential to fully understand molecular processes in confined cell compartments and will offer clues on the behaviour of simple confined systems, such as protocells and lipid-vesicle based devices. Using a model system composed of lipid vesicles, a membrane impermeable receptor and a membrane-permeable ligand, we have studied in detail how compartmentalization modulates the interaction between the confined receptor and its ligand. We demonstrate that confinement of one of the building blocks stabilizes complex self-assembled structures to the extent that dilution leads, counterintuitively, to the formation of long range assemblies. The behaviour of the system can be explained by considering a confinement factor that is analogous, although not identical, to the effective molarity for intramolecular binding events. The confinement effect renders complex self-assembled species robust and persistent under conditions where they do not form in bulk solution. Moreover, we show that the formation of stable complex assemblies in systems compartmentalized by semi-permeable membranes does not require the prior confinement of all components, but only that of key membrane impermeable building blocks. To use a macroscopic analogy, lipid vesicles are like ship-in-a bottle constructs that are capable of directing the assembly of the confined ship following the confinement of a few key wooden planks. Therefore, we believe that the confinement effect described here would have played an important role in shaping the increase of chemical complexity within protocells during the first stages of abiogenesis. Additionally, we argue that this effect can be exploited to design increasingly efficient functional devices based on comparatively simple vesicles for applications in biosensing, nanoreactors and drug delivery vehicles.
RESUMEN
It is highly desirable that supramolecular polymers self-assemble following small changes in the environment. The degree of responsiveness depends on the degree of cooperativity at play during the assembly. Understanding how to modulate and quantify cooperativity is therefore highly desirable for the study and design of responsive polymers. Here we show that the cooperative assembly of a porphyrin-based, double-stranded polymer is triggered by changes in building blocks and in salt concentration. We develop a model that accounts for this responsiveness by assuming the binding of the salt countercations to the double-stranded polymer. Using our assembly model we generate plots that show the increase in concentration of polymer versus the normalized concentration of monomer. These plots are ideally suited to appreciate changes in cooperativity, and show that, for our system, these changes are consistent with the increase in polymer length observed experimentally. Unexpectedly, we find that polymer stability increases when cooperativity decreases. We attribute this behaviour to the fact that increasing salt concentration stabilizes the overall polymer more than the nucleus. In other words, the cooperativity factor α, defined as the ratio between the growth constant Kg and the nucleation constant Kn decreases as the overall stability of the polymer increases. Using our model to simulate the data, we generate cooperativity plots to explore changes in cooperativity for multistranded polymers. We find that, for the same pairwise association constants, the cooperativity sharply increases with the number of strands in the polymer. We attribute this dependence to the fact that the larger the number of strands, the larger is the nucleus necessary to trigger polymer growth. We show therefore that the cooperativity factor α does not properly account for the cooperativity behaviour of multistranded polymers, or any supramolecular polymer with a nucleus composed of more than 2 building blocks, and propose the use of the corrected cooperativity factor αm. Finally, we show that multistranded polymers display highly cooperative polymerisation with pairwise association constants as low as 10 M-1 between the building blocks, which should simplify the design of responsive supramolecular polymers.
RESUMEN
All-or-nothing molecular assembly events, essential for the efficient regulation of living systems at the molecular level, are emerging properties of complex chemical systems that are largely attributed to the cooperativity of weak interactions. The link between the self-assembly and the interactions responsible for the assembly is however often poorly defined. In this work we demonstrate how the chelate effect (multivalence cooperativity) can play a central role in the regulation of the all-or-nothing assembly of structures (supramolecular polymers here), even if the building blocks are not multivalent. We have studied the formation of double-stranded supramolecular polymers formed from Co-metalloporphyrin and bi-pyridine building blocks. Their cooperative nucleation-elongation assembly can be summarized as a thermodynamic cycle, where the monomer weakly oligomerizes linearly or weakly dimerizes laterally. But thanks to the chelate effect, the lateral dimer readily oligomerizes linearly and the oligomer readily dimerizes laterally, leading to long double stranded polymers. A model based on this simple thermodynamic cycle can be applied to the assembly of polymers with any number of strands, and allows for the determination of the length of the polymer and the all-or-nothing switching concentration from the pairwise binding constants. The model, which is consistent with the behaviour of supramolecular polymers such as microtubules and gelators, clearly shows that all-or-nothing assembly is triggered by a change in the mode of assembly, from non-multivalent to multivalent, when a critical concentration is reached. We believe this model is applicable to many molecular assembly processes, ranging from the formation of cell-cell focal adhesion points to crystallization.