design of stimuli-responsive biomaterials based on PAs
Development of soft materials that mimic the ability of living organisms to sense the changes in their environment through various signals and respond in a way that optimizes processes is one of the challenges in emerging fields of biomedicine, soft robotics and energy materials. For a long time, we have relied on polymeric materials in countless industries for their high kinetic and thermodynamic stability, but recent efforts to create a more sustainable and environment-friendly future have cast a negative shadow on polymeric materials for their same property. As a result, the field of supramolecular polymers started to gain increasing attention. Supramolecular polymers, where the building blocks of the material assemble via non-covalent interactions to form a dynamic material, can have mechanical properties of plastics but also provide ease of processability, recycling and self-healing due to their reversible nature.
Interestingly, the concept of supramolecular polymers is far from new; in living systems, proteins in the extracellular matrix (ECM) dynamically form long, ordered supramolecular fibrils and depolymerize for vital cell functions. In the same manner, such specific inter and intramolecular interactions can be utilized to rationally design materials using bottom-up approaches. In this context, biomimetic multifunctional materials can be designed by using building blocks, such as peptide-based motifs and conjugates with organic and inorganic molecules, that predictably self-assemble and interact to generate functions similar to or surpassing those of natural products. For example, peptide amphiphiles are biomolecules made up of hydrophobic alkyl chains and a peptide sequence containing β-sheet forming amino acid residues that self-assemble in solution to form supramolecular nanofibers with long-range order. Because of their increased stability due to strong intermolecular hydrogen bonding interactions, these nanofibers provide excellent scaffolds for development of stimuli-responsive materials.
In different projects, we investigated their self-assembly in solution, secondary structure formation and interaction with water and ions in solution.
References
2023
Peptide Amphiphiles as Biodegradable Adjuvants for Efficient Retroviral Gene Delivery
Kubra Kaygisiz, Lena Rauch-Wirth, Aysenur Iscen, and 5 more authors
Abstract Retroviral gene delivery is the key technique for in vitro and ex vivo gene therapy. However, inefficient virion-cell attachment resulting in low gene transduction efficacy remains a major challenge in clinical applications. Adjuvants for ex vivo therapy settings need to increase transduction efficiency while being easily removed or degraded post-transduction to prevent the risk of venous embolism after infusing the transduced cells back to the bloodstream of patients, yet no such peptide system have been reported thus far. In this study, peptide amphiphiles (PAs) with a hydrophobic fatty acid and a hydrophilic peptide moiety that reveal enhanced viral transduction efficiency are introduced. The PAs form β-sheet-rich fibrils that assemble into positively charged aggregates, promoting virus adhesion to the cell membrane. The block-type amphiphilic sequence arrangement in the PAs ensures efficient cell-virus interaction and biodegradability. Good biodegradability is observed for fibrils forming small aggregates and it is shown that via molecular dynamics simulations, the fibril-fibril interactions of PAs are governed by fibril surface hydrophobicity. These findings establish PAs as additives in retroviral gene transfer, rivalling commercially available transduction enhancers in efficiency and degradability with promising translational options in clinical gene therapy applications.
2020
Light-Driven Expansion of Spiropyran Hydrogels
Chuang Li, Aysenur Iscen, Liam C. Palmer, and 2 more authors
Journal of the American Chemical Society, May 2020
The development of synthetic structures that mimic mechanical actuation in living matter such as autonomous translation and shape changes remains a grand challenge for materials science. In living systems the integration of supramolecular structures and covalent polymers contributes to the responsive behaviour of membranes, muscles and tendons, among others. Here we describe hybrid light-responsive soft materials composed of peptide amphiphile supramolecular polymers chemically bonded to spiropyran-based networks that expel water in response to visible light. The supramolecular polymers form a reversibly deformable and water-draining skeleton that mechanically reinforces the hybrid and can also be aligned by printing methods. The noncovalent skeleton embedded in the network thus enables faster bending and flattening actuation of objects, as well as longer steps during the light-driven crawling motion of macroscopic films. Our work suggests that hybrid bonding polymers, which integrate supramolecular assemblies and covalent networks, offer strategies for the bottom-up design of soft matter that mimics living organisms.
2019
Hofmeister Effects on Peptide Amphiphile Nanofiber Self-Assembly
Self-assembly is a process whereby molecules organize into structures with hierarchical order and complexity, often leading to functional materials. Biomolecules such as peptides, lipids and DNA are frequently involved in self-assembly, and this leads to materials of interest for a wide variety of applications in biomedicine, photonics, electronics, mechanics, etc. The diversity of structures and functions that can be produced provides motivation for developing theoretical models that can be used for a molecular-level description of these materials. Here we overview recently developed computational methods for modeling the self-assembly of peptide amphiphiles (PA) into supramolecular structures that form cylindrical nanoscale fibers using molecular-dynamics simulations. Both all-atom and coarse-grained force field methods are described, and we emphasize how these calculations contribute insight into fiber structure, including the importance of β-sheet formation. We show that the temperature at which self-assembly takes place affects the conformations of PA chains, resulting in cylindrical nanofibers with higher β-sheet content as temperature increases. We also present a new high-density PA model that shows long network formation of β-sheets along the long axis of the fiber, a result that correlates with some experiments. The β-sheet network is mostly helical in nature which helps to maintain strong interactions between the PAs both radially and longitudinally.
Light-Driven Expansion of Spiropyran HydrogelsJournal of the American Chemical Society, May 2020
Hofmeister Effects on Peptide Amphiphile Nanofiber Self-AssemblyThe Journal of Physical Chemistry B, Aug 2019