Melting transition in lipid vesicles functionalised by mobile DNA linkers

Abstract

We study phase behaviour of lipid-bilayer vesicles functionalised by ligand-receptor complexes made of synthetic DNA by introducing a modelling framework and a dedicated experimental platform. In particular, we perform Monte Carlo simulations that combine a coarse grained description of the lipid bilayer with state of art analytical models for multivalent ligand-receptor interactions. Using density of state calculations, we derive the partition function in pairs of vesicles and compute the number of ligand-receptor bonds as a function of temperature. Numerical results are compared to microscopy and fluorimetry experiments on large unilamellar vesicles decorated by DNA linkers carrying complementary overhangs. We find that vesicle aggregation is suppressed when the total number of linkers falls below a threshold value. Within the model proposed here, this is due to the higher configurational costs required to form inter-vesicle bridges as compared to intra-vesicle loops, which are in turn related to membrane deformability. Our findings and our numerical/experimental methodologies are applicable to the rational design of liposomes used as functional materials and drug delivery applications, as well as to study inter-membrane interactions in living systems, such as cell adhesion.

Programmable interactions with biomimetic DNA linkers at fluid membranes and interfaces

“…9a). This configuration is relevant to a number of experimental studies on equilibrium liposome-liposome [19,109] and liposome-SLB interactions [16], discussed in Sec. 3.1.…”

“…3.1). In many situations, however, the analytical approach turns out to be unfeasible, for example when attempting to model the reversible, temperature-dependent, self-assembly of relatively small LUVs in which thermal fluctuations have a large influence [109] (Sec. 3.1).…”

“…Importantly, Ref. [109] found that, to an excellent approximation, the overall interaction free energy, accounting for both the multivalent adhesion terms and the vesicle-deformation terms, increases linearly with the number of bridges formed. This results, along with results from MD simulations [192,193], could allow parametrising more coarsened models in which the effect of the deformability is implicitly accounted for.…”

Adaptable DNA interactions regulate surface triggered self assembly

“…† While the formation of inter-particle bridges induce particle-particle aggregation, a prominence of intra-particle loops tends to stabilise a colloidal gas phase. 24 Free-energy minimisation and combinatorial entropy demand the coexistence of inter-and intra-particle bonds. 11,17,[24][25][26] The equilibrium between the two bond-type populations can be systematically tuned by changing the total number of linkers and inert constructs per particle.…”

Coexistence of long and short DNA constructs within adhesion plaques

“…Building on our previous work on mimetic systems 9 , we functionalize the GUVs and the SLB with a binary mixture of DNA constructs that can bridge the two membranes and mediate adhesion. Such DNA constructs are particularly attractive because their length, flexibility and binding strength can be readily modified [14][15][16][17][18][19][20][21] . We support these experimental advances by extending the recently developed Monte Carlo scheme for modeling adhesion with multiple types of ligand-receptor pairs 13 , to modeling the formation of DNA bridges of different lengths.…”