Self‐assembling systems comprising intrinsically disordered protein polymers like elastin‐like recombinamers

Abstract

Despite lacking cooperatively folded structures under native conditions, numerous intrinsically disordered proteins (IDPs) nevertheless have great functional importance.These IDPs are hybrids containing both ordered and intrinsically disordered protein regions (IDPRs), the structure of which is highly flexible in this unfolded state. The conformational flexibility of these disordered systems favors transitions between disordered and ordered states triggered by intrinsic and extrinsic factors, folding into different dynamic molecular assemblies to enable proper protein functions. Indeed, prokaryotic enzymes present less disorder than eukaryotic enzymes, thus showing that this disorder is related to functional and structural complexity. Protein-based polymers that mimic these IDPs include the so-called elastin-like polypeptides (ELPs), which are inspired by the composition of natural elastin. Elastin-like recombinamers (ELRs) are ELPs produced using recombinant techniques and which can therefore be tailored for a specific application. One of the most widely used and studied characteristic structures in this field is the pentapeptide (VPGXG) n . The structural disorder in ELRs probably arises due to the high content of proline and glycine in the ELR backbone, because both these amino acids help to keep the polypeptide structure of elastomers disordered and hydrated. Moreover, the recombinant nature of these systems means that different sequences can be designed, including bioactive domains, to obtain specific structures for each application. Some of these structures, along with their applications as IDPs that self-assemble into functional vesicles or micelles from diblock copolymer ELRs, will be studied in the following sections. The incorporation of additional order-and disorder-promoting peptide/protein domains, such as α-helical coils or β-strands, in the ELR sequence, and their influence on self-assembly, will also be reviewed. In addition, chemically cross-linked systems with controllable order-disorder balance, and their role in biomineralization, will be discussed. Finally, we will review different multivalent IDPs-based coatings and films for different biomedical applications, such as spatially controlled cell adhesion, osseointegration, or biomaterial-associated infection (BAI).

Flexible customization of the self‐assembling abilities of short elastin‐like peptide Fn analogs by substituting N‐terminal amino acids

“…[39,40] Therefore, ELPs are regarded as intrinsically disordered proteins (IDPs) that retain functionality despite the lack of a single orderly structure. [41,42] Even in nonrandom structures above T t , ELPs can exist as a wide range of protein structures, including those partially structured in the form of premolten globules or molten globules rather than a single ordered structure. [43] Therefore, substitution of guest residues can affect the self-assembling abilities of ELPs by altering the interactions between peptide molecules or between peptides and solvent molecules, instead of controlling the tertiary structure of ELPs.…”

Determining the Sequence Dependency of Self-Assembly of Elastin-Like Peptides Using Short Peptide Analogues with Shuffled Repetitive Sequences

“…T t is often used as an indicator of self-assembling ability, and the low T t value indicates potent self-assembling ability. 27,44,42 Although it is known that shortening the peptide length reduces the selfassembling property of ELPs, we found that short ELP analogues, namely, B and C, showing self-assembling properties could be obtained by using these potential motifs as a repetitive unit. On the other hand, three shuffled analogues, D, F, and L, hardly dissolved in the phosphate buffer.…”

“…Therefore, ELPs have been regarded as intrinsically disordered proteins (IDPs) that exhibit their functionality without forming a single orderly structure. 41,42 However, notably, some studies have mentioned that the turn structure that forms in the PG sequence is important for the self-assembly of ELPs. 43−45 On the other hand, it has been reported that the secondary structure of synthetic self-assembling ELPs is different from that of conventional ELP.…”

Tissue engineering modalities in skeletal muscles: focus on angiogenesis and immunomodulation properties

“…Exosomes (Exos), a subclass of extracellular vesicles, have a crucial role in paracrine cell-to-cell interaction via the transfer of several signaling biomolecules [ 280 , 281 ]. These particles with an average diameter size of 50–150 nm can promote angiogenesis in ischemic organs [ 282 ]. It has been shown that Exos lack oncogenic and immunogenic features and can cross biological interfaces and thus distribute easily in the whole body [ 283 ].…”