Mimicking enzyme function and increasing performance of naturally evolved proteins is one of the most challenging and intriguing aims of nanoscience. Here, we employ DNA nanotechnology to design a synthetic enzyme that substantially outperforms its biological archetypes. Consisting of only eight strands, our DNA nanostructure spontaneously inserts into biological membranes by forming a toroidal pore that connects the membrane’s inner and outer leaflets. The membrane insertion catalyzes spontaneous transport of lipid molecules between the bilayer leaflets, rapidly equilibrating the lipid composition. Through a combination of microscopic simulations and fluorescence microscopy we find the lipid transport rate catalyzed by the DNA nanostructure exceeds 107 molecules per second, which is three orders of magnitude higher than the rate of lipid transport catalyzed by biological enzymes. Furthermore, we show that our DNA-based enzyme can control the composition of human cell membranes, which opens new avenues for applications of membrane-interacting DNA systems in medicine.
Protein‐based fibers are used by nature as high‐performance materials in a wide range of applications, including providing structural support, creating thermal insulation, and generating underwater adhesives. Such fibers are commonly generated through a hierarchical self‐assembly process, where the molecular building blocks are geometrically confined and aligned along the fiber axis to provide a high level of structural robustness. Here, this approach is mimicked by using a microfluidic spinning method to enable precise control over multiscale order during the assembly process of nanoscale protein nanofibrils into micro‐ and macroscale fibers. By varying the flow rates on chip, the degree of nanofibril alignment can be tuned, leading to an orientation index comparable to that of native silk. It is found that the Young's modulus of the resulting fibers increases with an increasing level of nanoscale alignment of the building blocks, suggesting that the mechanical properties of macroscopic fibers can be controlled through varying the level of ordering of the nanoscale building blocks. Capitalizing on strategies evolved by nature, the fabrication method allows for the controlled formation of macroscopic fibers and offers the potential to be applied for the generation of further novel bioinspired materials.
The molecular origins of Alzheimer's disease are associated with the aggregation of the amyloidβ peptide (Aβ). This process is controlled by a complex cellular homeostasis system, which involves a variety of components, including proteins, metabolites and lipids. It has been shown in particular that certain components of lipid membranes can speed up Aβ aggregation. This observation prompts the question of whether there are protective cellular mechanisms to counterbalance this effect. Here, to address this issue, we investigate the role of the composition of lipid membranes in modulating the aggregation process of Aβ. By adopting a chemical kinetics approach, we first identify a panel of lipids that affect the aggregation of the 42-residues form of Aβ (Aβ42), ranging from enhancement to inhibition. We then show that these effects tend to average out in mixtures of these lipids, as such mixtures buffer extreme aggregation behaviors as the number of components increases. These results indicate that a degree of quality control on protein aggregation can be achieved through a mechanism by which an increase in the molecular complexity of lipid membranes balances opposite effects and creates resilience to aggregation.
Microcapsules are a key class of microscale materials with applications in areas ranging from personal care to biomedicine, and with increasing potential to act as extracellular matrix (ECM) models of hollow organs or tissues. Such capsules are conventionally generated from non-ECM materials including synthetic polymers. Here, we fabricated robust microcapsules with controllable shell thickness from physically-and enzymatically-crosslinked gelatin and achieved a core-shell architecture by exploiting a liquid-liquid phase separated aqueous dispersed phase system in a one-step microfluidic process. Microfluidic mechanical testing revealed that the mechanical robustness of thicker-shell capsules could be controlled through modulation of the shell thickness. Furthermore, the microcapsules demonstrated environmentally-responsive deformation, including buckling by osmosis and external mechanical forces. Finally, a sequential release of cargo species was obtained through the degradation of the capsules. Stability measurements showed the capsules were stable at 37 • C for more than two weeks. These smart capsules are promising models of hollow biostructures, microscale drug carriers, and building blocks or compartments for active soft materials and robots.
The self-assembly of the protein clathrin on biological membranes facilitates essential processes of endocytosis and has provided a source of inspiration for materials design by the highly ordered structural appearance. By mimicking the architecture of the protein building blocks and clathrin self-assemblies to coat liposomes with biomaterials, advanced hybrid carriers can be derived. Here, we present a method for fabricating DNA-coated liposomes by hydrophobically anchoring and subsequently connecting DNA-based triskelion structures on the liposome surface inspired by the assembly of the protein clathrin. Dynamic light scattering, ζpotential, confocal microscopy, and cryo-electron microscopy measurements independently demonstrate successful DNA coating. Nanomechanical measurements conducted with atomic force microscopy show that the DNA coating enhances the mechanical stability of the liposomes relative to uncoated ones. Furthermore, we provide the possibility to reverse the coating process by triggering the disassembly of the DNA coats through a toehold-mediated displacement reaction. Our results describe a straightforward, versatile, and reversible approach for coating and stabilizing lipid vesicles through the assembly of rationally designed DNA structures. This method has potential for further development toward the ordered arrangement of tailored functionalities on the surface of liposomes and for applications as hybrid nanocarriers.
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