Light-Triggered Self-Assembly of Peptide Nanoparticles into Nanofibers in Living Cells through Molecular Conformation Changes and H-Bond Interactions

Abstract

Controlled self-assembly has attracted extensive interest in biological and nanotechnological applications. Enzymatic or biocatalytic triggered self-assembly is widely used for the diagnostic and prognostic marker in different pathologies because of their nanostructures and biological effects. However, it remains a great challenge to control the self-assembly of peptides in living cells with a high degree of spatial and temporal precision. Here we demonstrate a lighttriggered platform that enables spatiotemporal control of self-assembly from nanoparticles into nanofibers in living cells through subtle molecular conformational changes and internal H-bonding interactions. The platform contained 3methylene-2-(quinolin-8-yl) isoindolin-1-one, which acts as the light-controlled unit to disrupt the hydrophilic/lipophilic balance through the change of molecular conformation, and a peptide that can be a faster recombinant to assemble via H-bonding interactions. The process has good biocompatibility because it does not involve waste generation or oxygen consumption; moreover, the assembly rate constant was fast and up to 0.17 min −1 . It is applied to the regulation of molecular assembly in living cells. As such, our findings demonstrate that light-triggered controllable assembly can be applied for initiative regulating cellular behaviors in living systems.

Self-assembly of peptide nanomaterials at biointerfaces: molecular design and biomedical applications

“…41 Currently, the in vivo self-assembly of peptides is typically achieved through endogenous stimuli, such as enzymes, pH, and redox reactions in specific physiological and pathological regions, or exogenous stimuli, such as light, sound, and temperature. [42][43][44][45][46][47][48] In recent years, numerous reviews have been published on the in vivo self-assembly strategies of stimuli-responsive peptides and their biomedical applications in areas such as tumor therapy, drug delivery, and antibacterial treatments. [49][50][51][52][53] However, under complex physiological conditions in vivo, due to the dynamic characteristics of selfassembled nanomaterials, changes in their morphology and structure in response to stimuli will affect their performance on the biological surface.…”

“…80,81 When the assembled peptide interacts with the protein, multiple hydrogen bonds formed between the amide bonds of the peptide main chain and each side chain group form a hydrogen bond array, inducing the orientation of the overall and active center of the protein. 45,82 This provides a basis for constructing protein assemblies with precise orientation. Eisenberg et al demonstrated that short peptide fragments with a β-sheet structure in amyloid can specifically co-assemble with the corresponding amyloid, driving the protein to transition from the native structure to the amyloid state.…”

Chiral supramolecular nanomaterials: From chirality transfer and amplification to regulation and applications

“…Sun et al reported a photoactivated system that allows precise manipulation of the arrangement of nanoparticles (NPs) into nanofibers within living cells by utilizing subtle alterations in molecular conformation and internal hydrogen bonding interactions. [ 58 ] The results indicate that the use of light‐induced controllable assembly can be employed to actively regulate cellular behaviors in living organisms. Nieland et al demonstrated the creation of various dissipative or metastable dynamic covalent systems by utilizing photons as a trigger, enabling manipulation of the quantity of monomers engaged in cyclo‐oligomerization, resulting in both ring contraction and expansion.…”

Intracellular Hyperbranched Polymerization for Circumventing Cancer Drug Resistance

“…The cellular environment is rich in biological macromolecules and reactive species, which inspires chemists to artificially perform various chemical reactions in cells for physiological purposes. − Among all of these artificial reactions, intracellular chemical polymerization represents a sparkling frontier. Small monomers can undergo in situ polymerization in a miniature “lab”, achieving prolonged retention for the products and adequately regulating cell behavior. − Despite a few studies based on intracellular polymerization, such as radical polymerization, − condensation polymerization, and electroactive polymerization, conducting polymerization inside living cells remains an appealing yet significantly challenging task. For instance, abundant oxygen and amino acids in cells may inevitably cause side reactions and even quench the polymerization process.…”