Controlling Self-Assembly Kinetics of DNA-Functionalized Liposomes Using Toehold Exchange Mechanism

Abstract

The selectivity of Watson-Crick base pairing has allowed the design of DNA-based functional materials bearing an unprecedented level of accuracy. Examples include DNA origami, made of tiles assembling into arbitrarily complex shapes, and DNA coated particles featuring rich phase behaviors. Frequently, the realization of conceptual DNA-nanotechnology designs has been hampered by the lack of strategies for effectively controlling relaxations. In this article, we address the problem of kinetic control on DNA-mediated interactions between Brownian objects. We design a kinetic pathway based on toehold-exchange mechanisms that enables rearrangement of DNA bonds without the need for thermal denaturation, and test it on suspensions of DNA-functionalized liposomes, demonstrating tunability of aggregation rates over more than 1 order of magnitude. While the possibility to design complex phase behaviors using DNA as a glue is already well recognized, our results demonstrate control also over the kinetics of such systems.

Pathway Diversity in the Self-Assembly of DNA-Derived Bioconjugates

“…The initial gradual decrease in absorption from 20 to 50 °C is probably due to sedimentation of large network aggregates. 44 Between 50 and 65 °C, a stepwise recovery of the signal takes place until the same value is reached as in the heating curve (cf. Figure 2A) of the mixed polymer poly(Py-a/Py-b).…”

Communication: Free energy of ligand-receptor systems forming multimeric complexes

“…• C. 13 We use our framework to calculate the free energy of the system, and demonstrate that, despite the large effect on aggregation kinetics, changing χ has little consequences on the thermodynamic ground state of the system. The DNA tethers are again modelled as freely pivoting rigid rods of length L = 10 nm, with freely diffusing tethering points and point-like sticky ends.…”

“…13. Let us consider a suspension of identical micron-size lipid vesicles, functionalized by three families of mobile DNA linkers with sticky ends here labelled as γ, δ 1 , and δ 2 .…”

“…[3][4][5][6][7][8][9][10][11] Many functionalization schemes rely on one-to-one ligand-receptor interactions, but recently, designs featuring multi-linker complexation have been proposed to extend the accessible range of functionalities. 9,[12][13][14][15] In particular, Parolini et al 13 adopted three-linker complexes enabling toehold-mediated strand exchange reactions 16 to control aggregation kinetics of lipid vesicles coated with DNA linkers. Halverson and Tkachenko 12 also proposed the use of three-linker DNA complexes to program a cooperative behavior between functionalized particles, which could allow to control the sequence of binding events in the self-assembly.…”

“…IV, we examine the suspensions of DNA-functionalized vesicles of Ref. 13, discussing the thermodynamic ground state in relation to the kinetic behaviour characterized in the original publication.…”