Order from Disorder with Intrinsically Disordered Peptide Amphiphiles

Abstract

Amphiphilic molecules and their self-assembled structures have long been the target of extensive research due to their potential applications in fields ranging from materials design to biomedical and cosmetic applications. Increasing demands for functional complexity have been met with challenges in biochemical engineering, driving researchers to innovate in the design of new amphiphiles. An emerging class of molecules, namely, peptide amphiphiles, combines key advantages and circumvents some of the disadvantages of conventional phospholipids and block copolymers. Herein, we present new peptide amphiphiles composed of an intrinsically disordered peptide conjugated to two variants of hydrophobic dendritic domains. These molecules, termed intrinsically disordered peptide amphiphiles (IDPA), exhibit a sharp pH-induced micellar phase-transition from low-dispersity spheres to extremely elongated worm-like micelles. We present an experimental characterization of the transition and propose a theoretical model to describe the pH-response. We also present the potential of the shape transition to serve as a mechanism for the design of a cargo hold-and-release application. Such amphiphilic systems demonstrate the power of tailoring the interactions between disordered peptides for various stimuli-responsive biomedical applications.

3D-printed SAXS chamber for controlled in situ dialysis and optical characterization

“…To show reversibility, we used a pH-responsive system of intrinsically disordered peptide amphiphiles [IDPAs (Jacoby et al, 2021)]. Specific amino acids in the used sequence can get protonated and become uncharged with decreasing pH.…”

In-Silico Analysis of pH-Dependent Liquid-Liquid Phase Separation in Intrinsically Disordered Proteins

“…In recent work, we accounted for the effect of pH on the solubility [ 20 ] and disorder state [ 21 ] of IDPs using different equations that simultaneously consider the impact of the pH on sequence hydrophobicity and net charge. This allowed us to develop two novel bioinformatic tools to predict pH-dependent solubility and disorder: SolupHred [ 22 ] and DispHScan [ 23 ], respectively, which recapitulate previous and novel experimental data [ 24 , 25 , 26 ]. The solubility and degree of disorder of a protein at given pH influence its propensity to phase-separate, but large-scale analyses exploring these connections are scarce.…”

Self-Assembly of Tunable Intrinsically Disordered Peptide Amphiphiles

“…In this context, intrinsically disordered peptide amphiphiles (IDPAs) are of great interest as they combine building blocks from natural lipids and proteins. − IDPAs are composed of intrinsically disordered peptides conjugated to hydrocarbon chains, creating amphiphiles with polymeric headgroups and hydrophobic anchors that remain compatible with natural lipid membranes. Though IDPAs hold promise for fine-tuned nanoscopic self-assembly, the sequence space of even a 20 amino acid short polypeptide is extremely large and hardly explored.…”