Pathway‐Dependent Co‐Assembly of Elastin‐Like Polypeptides

Abstract

In natural systems, temperature‐induced assembly of biomolecules can lead to the formation of distinct assembly states, created out of the same set of starting compounds, based on the heating trajectory followed. Until now it has been difficult to achieve similar behavior in synthetic polymer mixtures. Here, a novel pathway‐dependent assembly based on stimulus‐responsive polymers is shown. When a mixture of mono‐ and diblock copolymers, based on elastin‐like polypeptides, is heated with a critical heating rate co‐assembled particles are created that are monodisperse, stable, and have tunable hydrodynamic radii between 20 and 120 nm. Below this critical heating rate, the constituents separately form polymer assemblies. This process is kinetically driven and reversible in thermodynamically closed systems. Using the co‐assembly pathway, fluorescent proteins and bioluminescent enzymes are encapsulated with high efficiency. Encapsulated cargo shows unperturbed function even after delivery into cells. The pathway‐dependent co‐assembly of elastin‐like polypeptides is not only of fundamental interest from a materials science perspective, allowing the formation of multiple distinct assemblies from the same starting compounds, which can be interconverted by going back to the molecularly dissolved states. It also enables a versatile way for constructing highly effective vehicles for the cellular delivery of biomolecular cargo.

Self‐Assembly or Coassembly of Multiresponsive Histidine‐Containing Elastin‐Like Polypeptide Block Copolymers

“…ELP 2 was previously produced and characterized by Pille et al. [ 21 ] ELP2 was shown to form nanoparticles at nanomolar concentrations when heated above the T t of the hydrophobic block. Table 4 shows a brief comparison between both ELP diblocks.…”

“…The ELP [A 3 G 2 ‐60][I‐60] was kindly provided by Jan Pille and produced according to a literature description. [ 21 ]…”

“…This method was also used to form coassembly coacervates of ELP monoblocks and diblocks with the potential for encapsulation of bioactive macromolecular cargo. [ 20,21 ]…”

Spatiotemporal Dynamic Assembly/Disassembly of Organelle‐Mimics Based on Intrinsically Disordered Protein‐Polymer Conjugates

“…Altogether, we believe these findings of spatially localized co‐assembly of the monoblock ELP and ELP‐polymer conjugates will enable a facile and versatile way for interfacial constructing functional organelle mimics. [ 24 ]…”

Broadening Approaches in Nanoparticle Synthesis Through Elastin-Like Polypeptides

“…This drug-polypeptide conjugate was able to form 100 nm nanoparticles and deliver their chemotherapeutic payload in a murine cancer model, inducing an almost completely tumor regression after a single dose. ELPs engineering also can serve as a straightforward way to incorporate protein-based targeting agents or encapsulate the protein of interest with high efficiency (van Oppen et al, 2019;Pille et al, 2021).…”