Force and time-dependent self-assembly, disruption and recovery of supramolecular peptide amphiphile nanofibers

Abstract

Biological feedback mechanisms exert precise control over the initiation and termination of molecular self-assembly in response to environmental stimuli, while minimizing the formation and propagation of defects through self-repair processes. Peptide amphiphile (PA) molecules can self-assemble at physiological conditions to form supramolecular nanostructures that structurally and functionally resemble the nanofibrous proteins of the extracellular matrix, and their ability to reconfigure themselves in response to external stimuli is crucial for the design of intelligent biomaterials systems. Here, we investigated real-time self-assembly, deformation, and recovery of PA nanofibers in aqueous solution by using a force-stabilizing double-pass scanning atomic force microscopy imaging method to disrupt the self-assembled peptide nanofibers in a force-dependent manner. We demonstrate that nanofiber damage occurs at tip-sample interaction forces exceeding 1 nN, and the damaged fibers subsequently recover when the tip pressure is reduced. Nanofiber ends occasionally fail to reconnect following breakage and continue to grow as two individual nanofibers. Energy minimization calculations of nanofibers with increasing cross-sectional ellipticity (corresponding to varying levels of tip-induced fiber deformation) support our observations, with high-ellipticity nanofibers exhibiting lower stability compared to their non-deformed counterparts. Consequently, tip-mediated mechanical forces can provide an effective means of altering nanofiber integrity and visualizing the self-recovery of PA assemblies.

Polyethylene Glycol–Based Polymer-Drug Conjugates: Novel Design and Synthesis Strategies for Enhanced Therapeutic Efficacy and Targeted Drug Delivery

“…Polymer-drug conjugates' thermal behaviour and phase transitions are assessed using DSC. Any modifications in the melting point or thermal stability brought on by drug conjugation can be detected [123].…”

Large-range high-speed dynamic-mode atomic force microscope imaging: adaptive tapping towards minimal force

“…For example, the time-delay in deciphering the TA can be reduced, and thereby, the sample topography can be better estimated by observer-based techniques [19][20][21]. Recent efforts in improving the performance or functionality of tapping-mode or peak-force mode imaging also include the double-pass scanning method [22] to compensate for the cantilever deflection drift and environmental disturbance (e.g. hydrodynamic force in liquid imaging), and the peakforce quantitative nanomechanics technique [2,3] that combines peak force imaging with infrared reflection mapping to simultaneously map sample topography and chemical-mechanical properties of the sample.…”

Modular Platform of Carbohydrates-modified Supramolecular Polymers Based on Dendritic Peptide Scaffolds

“…For example, the assembly and disassembly of microtubules constructed by tubulins are dynamic and reversible, which is critical for microtubules to support the morphology and movement of cells and control the directional movement of intracellular particles and organelles . Inspired by the important role of supramolecular architectures in biological systems, many artificial supramolecular biomaterials with impressive properties and functions have been developed for biomedical applications. − In the past decades, peptide-based assemblies have received extensive attention due to their biomimetic chemical and mechanical properties, high biodegradability, and good biocompatibility. − Since the first example of supramolecular polymers based on amphiphilic peptide molecules was reported by Stupp and co-workers, various supramolecular interactions have been successively applied to peptide-based self-assembly systems, resulting in spherical, cylindrical, sheet and tubular polypeptide assemblies. − Meanwhile, well-established synthetic methods of peptide building blocks enable the introduction of other biomolecules, such as nucleic acids, lipids, and carbohydrates, for transducing biological signals and modulating cellular behavior. − Among them, the carbohydrate-peptide supramolecular polymers are especially highlighted by the structural diversity and complexity. − Moreover, carbohydrates play an important role in mediating intercellular communication and modulating immune responses, , and small molecular glycopeptides show excellent properties in anti-pathogen and intracellular delivery. − Therefore, the glycopeptide supramolecular polymers with multivalent presentation of carbohydrates are highly available for the fabrication of immune-relevant biomaterials to address cancer, bacterial and viral pathogens. , However, due to the complexity of carbohydrates, the generation of appropriate glycopeptide monomers is the foundation as well as the limiting step of fabricating diverse glycopeptide supramolecular polymers. − Therefore, a modular approach to present the various carbohydrates, especially oli...…”