Colloidal LEGO with peptides; Orthogonal self-assembly of peptide-functionalized colloids

The aim of this project is to control the hierarchical and reversible assembly of complex mixtures of micron-sized colloids directed by the specific recognition of orthogonal coiled-coil peptides.

 

COlloidal LEGO

The complex and hierarchical structures that form the basis of life are formed spontaneously through self-assembly of small building blocks. Crucial for the proper functioning of living self-assembling systems are i) high specificity in the interactions, to allow the orthogonal creation of widely different structures in a mixture that contains a vast variety of building blocks, ii) reversibility of the assemblies, to ensure thermal annealing of “flaws” within the structure and thus guaranteeing high-fidelity in their function and iii) directionality of the bonds that form the skeleton of the structures, thus allowing the formation of anisotropic structures, which possess a polarity that is essential in generating forces or transducing biological signals.

n this project we take inspiration from nature by exploring the self-assembly of colloidal particles using one of nature’s own molecular recognition motifs; the coiled-coil peptides. Anchoring these coiled-coil peptides onto the surface of micron-sized colloidal particles allows them to be self-assembled by triggering the heterodimeric coiled-coil formation following a temperature or ionic strength quench. The specificity (requirement i) is inherent in the coiled-coil motif, and will be exploited by studying the self-assembly behaviour of mixtures of colloids, each decorated with another co-complementary pair of peptides, going up to mixtures containing 8 different species of colloidal particles, and thus 4 different pairs that interact selectively. Depending on the depth and rate of quenching into the binding regime, either equilibrium structures, such as colloidal crystals, for slow & mild quenches, or non-equilibrium structures, such as gels, for fast & deep quenches can be expected. This allows us to study, using a combination of novel peptide and colloid chemistry, microscopy and single-molecule force spectroscopy when reversibility (requirement ii) is attained. Moreover, as the different coiled-coil sequences have different melting temperatures, we can trigger the selective assembly of subsets of the complex mixture, mimicking the triggered and selective assembly of complex structures in biological systems. Finally, we will explore the use of anisotropic colloids, in which for example only a half of the particle is functionalized with coiled-coil peptides, to explore the realm of directionality (requirement iii) in the interactions. Ultimately the goal of this project is to explore the use of coiled-coil peptides in the generation of complex and hierarchical structures, unravel the mechanisms underlying the accomplishment of reversible interactions and bridge the length scales from the molecular, to the colloidal and ultimately the macroscopic domain.