Abstract
The dynamic interactions of membranes, particularly their fusion and fission, are critical for the transmission of chemical information between cells. Fusion is primarily driven by membrane tension built up through membrane deformation. For artificial polymersomes, fusion is commonly induced via the external application of a force field. Herein, fusion-promoted development of anisotropic tubular polymersomes (tubesomes) was achieved in the absence of an external force by exploiting the unique features of aqueous ring-opening metathesis polymerization-induced self-assembly (ROMPISA). The out-of-equilibrium tubesome morphology was found to arise spontaneously during polymerization, and the composition of each tubesome sample (purity and length distribution) could be manipulated simply by targeting different core-block degrees of polymerization (DPs). The evolution of tubesomes was shown to occur via fusion of “monomeric” spherical polymersomes, evidenced most notably by a step-growth-like relationship between the fraction of tubular to spherical nano-objects and the average number of fused particles per tubesome (analogous to monomer conversion and DP, respectively). Fusion was also confirmed by Förster resonance energy transfer (FRET) studies to show membrane blending and confocal microscopy imaging to show mixing of the polymersome lumens. We term this unique phenomenon polymerization-induced polymersome fusion, which operates via the buildup of membrane tension exerted by the growing polymer chains. Given the growing body of evidence demonstrating the importance of nanoparticle shape on biological activity, our methodology provides a facile route to reproducibly obtain samples containing mixtures of spherical and tubular polymersomes, or pure samples of tubesomes, of programmed length. Moreover, the capability to mix the interior aqueous compartments of polymersomes during polymerization-induced fusion also presents opportunities for its application in catalysis, small molecule trafficking, and drug delivery.
Highlights
The fusion of biological membranes is an essential process governing endo- and exocytosis, protein trafficking, fertilization, and viral infection in eukaryotic cells.[1−3] Proteins and othermolecules are distributed throughout a cell, released into or internalized from the extracellular space via the action of membrane-bound vesicles.[4]
Vesicle fusion is contingent on the action of proteins in biological systems, dissipative particle dynamics (DPD) simulations have shown that fusion between vesicles can occur spontaneously in the absence of proteins when two criteria are satisfied: (1) the particles can adhere to one another and maintain close contact and (2) there is sufficient membrane tension to overcome energetic barriers of fusion, of which the membrane bending energy dominates.[12]
While several strategies have been developed far to generate water-soluble Ru-based metathesis catalysts, often through transformations involving either N-heterocyclic carbene (NHC) or pyridine ligands,[60,61] such catalysts typically suffer from reduced activity compared to the unmodified precursor in organic solvent.[62]
Summary
The fusion of biological membranes is an essential process governing endo- and exocytosis, protein trafficking, fertilization, and viral infection in eukaryotic cells.[1−3] Proteins and other (macro)molecules are distributed throughout a cell, released into or internalized from the extracellular space via the action of membrane-bound vesicles.[4]. The mechanisms of vesicle budding and fusion require an input of energy to occur In biological systems, this energy is supplied by “SNAP REceptor”, SNARE, proteins, which bring vesicles into close contact with the target surface and induce deformations in their membranes.[6−9] The tension built up through such elastic deformations is hypothesized to serve as the main driving force for vesicle fusion,[10] originating from an overall reduction in the tension-induced bending energy (Eb) of the system upon each fusion event.[11]. Vesicle fusion is contingent on the action of proteins in biological systems, dissipative particle dynamics (DPD) simulations have shown that fusion between vesicles can occur spontaneously in the absence of proteins when two criteria are satisfied: (1) the particles can adhere to one another and maintain close contact and (2) there is sufficient membrane tension to overcome energetic barriers of fusion, of which the membrane bending energy dominates.[12] The bending energy of a membrane (Eb) is defined in eq 1
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