Self-Assembling Micelles Based on an Intrinsically Disordered Protein Domain

Abstract

The self-assembly of micellar structures from di-block polymers that contain hydrophilic and hydrophobic domains has been of great interest for the encapsulation of drugs and other hydrophobic molecules. While most commercially used surfactants are derived from hydrocarbon sources, there have been recent efforts to replace these with biodegradable, non-toxic, biologically synthesized alternatives. Previous examples have primarily examined naturally occurring self-assembling-proteins, such as silk and elastin-like sequences. Herein, we describe a new series of fusion proteins that have been developed to self-assemble spontaneously into stable micelles that are 27 nm in diameter after enzymatic cleavage of a solubilizing protein tag. The sequences of the proteins are based on a human intrinsically disordered protein, which has been appended with a hydrophobic segment. The micelles were found to form across a broad range of pH, ionic strength, and temperature conditions, with critical micelle concentration (CMC) values below 1 µM being observed in some cases. The reported micelles were found to solubilize hydrophobic metal complexes and organic molecules, suggesting their potential suitability for catalysis and drug delivery applications. Furthermore, the inherent flexibility in the design of these protein sequences enables the encoding of additional functionalities for many future applications. Overall, this work represents a new biomolecular alternative to traditional surfactants that are based on non-renewable and poorly biodegradable hydrocarbon sources.

A mechanism for reversible mesoscopic aggregation in liquid solutions

“…The mesoscopic clusters are not micelle 23 -like objects. This is evidenced by the fact that the mole fraction of the clusters increases gradually with the concentration of the solute, the latter concentration showing no saturation; the value of the mole fraction is consistent with estimates of the free energy cost of creating bulk solute-rich liquid 11 .…”

Folding and self-assembly of short intrinsically disordered peptides and protein regions

“…Finally, no obvious trends were observed aer changing different salt concentrations. 52 Acosta et al proposed the use of antimicrobial peptides (AMPs) as self-assembling domains to drive hierarchical organization of intrinsically disordered protein polymers (IDPPs) based on an elastin-like recombinamer (ELR) (Val-Pro-Gly-Ser-Gly) 50 -(Ile-Pro-Gly-Val-Gly) 60 . At 5 C, the ELR alone did not form any nanostructure.…”

Thermosensitive Vesicles from Chemically Encoded Lipid‐Grafted Elastin‐like Polypeptides

“…[21,22] Francis lab also reported series of fusion proteins that have been developed to self-assemble spontaneously into stable micelles after enzymatic cleavage of asolubilizing protein tag. [23] Natural lipidated proteins are reference models for the development of relevant artificial lipid-protein conjugates due to their diverse properties,s uch as bioactivity,s elfassembly and cell membrane anchoring properties that can regulate different cellular functions. [24] In this context, Chilkotisgroup has firstly produced post-translationally modified ELPs conjugates with cholesterol [25] and aliphatic myristoyl group, [26] exhibiting temperature-triggered self-assembly into ad iverse array of structures including fibers,b eads-on-astring coacervates,a nd networks of fibers.I na ddition, the production of different derivatives of linear lipid-ELPs via post-translational modification, self-assembly into micelles, [27,28] elongated fibers and bottle-brush structures, [29] have also been reported recently by Mozhdehi et al Nevertheless,none of these previous studies using linear lipid-ELP bioamphiphiles have shown or investigated their membrane forming property.…”

“…Champion's lab developed another approach to access protein vesicles from ELPs, especially using charge interactions with peptide zippers [21, 22] . Francis’ lab also reported series of fusion proteins that have been developed to self‐assemble spontaneously into stable micelles after enzymatic cleavage of a solubilizing protein tag [23] …”