publications

2024

1. 

   Multiscale Simulations of Self-Assembling Peptides: Surface and Core Hydrophobicity Determine Fibril Stability and Amyloid Aggregation

   Aysenur Iscen, Kübra Kaygisiz, Christopher V. Synatschke, and 2 more authors

   Biomacromolecules, May 2024

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   Assemblies of peptides and proteins through specific intermolecular interactions set the basis for macroscopic materials found in nature. Peptides provide easily tunable hydrogen-bonding interactions, which can lead to the formation of ordered structures such as highly stable β-sheets that can form amyloid-like supramolecular peptide nanofibrils (PNFs). PNFs are of special interest, as they could be considered as mimics of various fibrillar structures found in nature. In their ability to serve as supramolecular scaffolds, they could mimic certain features of the extracellular matrix to provide stability, interact with pathogens such as virions, and transduce signals between the outside and inside of cells. Many PNFs have been reported that reveal rich bioactivities. PNFs supporting neuronal cell growth or lentiviral gene transduction have been studied systematically, and their material properties were correlated to bioactivities. However, the impact of the structure of PNFs, their dynamics, and stabilities on their unique functions is still elusive. Herein, we provide a microscopic view of the self-assembled PNFs to unravel how the amino acid sequence of self-assembling peptides affects their secondary structure and dynamic properties of the peptides within supramolecular fibrils. Based on sequence truncation, amino acid substitution, and sequence reordering, we demonstrate that peptide–peptide aggregation propensity is critical to form bioactive β-sheet-rich structures. In contrast to previous studies, a very high peptide aggregation propensity reduces bioactivity due to intermolecular misalignment and instabilities that emerge when fibrils are in close proximity to other fibrils in solution. Our multiscale simulation approach correlates changes in biological activity back to single amino acid modifications. Understanding these relationships could lead to future material discoveries where the molecular sequence predictably determines the macroscopic properties and biological activity. In addition, our studies may provide new insights into naturally occurring amyloid fibrils in neurodegenerative diseases.

2023

1. Peptide Amphiphiles as Biodegradable Adjuvants for Efficient Retroviral Gene Delivery

   Kubra Kaygisiz, Lena Rauch-Wirth, Aysenur Iscen, and 5 more authors

   Advanced Healthcare Materials, May 2023

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   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.

2. Determining glass transition in all-atom acrylic polymeric melt simulations using machine learning

   Atreyee Banerjee, Aysenur Iscen, Kurt Kremer, and 1 more author

   The Journal of Chemical Physics, Aug 2023

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   The functionality of many polymeric materials depends on their glass transition temperatures (Tg). In computer simulations, Tg is often calculated from the gradual change in macroscopic properties. Precise determination of this change depends on the fitting protocols. We previously proposed a robust data-driven approach to determine Tg from the molecular dynamics simulation data of a coarse-grained semiflexible polymer model. In contrast to the global macroscopic properties, our method relies on high-resolution microscopic details. Here, we demonstrate the generality of our approach by using various dimensionality reduction and clustering methods and apply it to an atomistic model of acrylic polymers. Our study reveals the explicit contribution of the side chain and backbone residues in influencing the determination of the glass transition temperature.

3. 

   Molecular Simulation Strategies for Understanding the Degradation Mechanisms of Acrylic Polymers

   Aysenur Iscen, Nancy C. Forero-Martinez, Omar Valsson, and 1 more author

   Macromolecules, May 2023

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4. 

   Role of supramolecular polymers in photo-actuation of spiropyran hydrogels

   Chuang Li, Qinsi Xiong, Tristan D. Clemons, and 7 more authors

   Chem. Sci., May 2023

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   Supramolecular-covalent hybrid polymers have been shown to be interesting systems to generate robotic functions in soft materials in response to external stimuli. In recent work supramolecular components were found to enhance the speed of reversible bending deformations and locomotion when exposed to light. The role of morphology in the supramolecular phases integrated into these hybrid materials remains unclear. We report here on supramolecular-covalent hybrid materials that incorporate either high-aspect-ratio peptide amphiphile (PA) ribbons and fibers, or low-aspect-ratio spherical peptide amphiphile micelles into photo-active spiropyran polymeric matrices. We found that the high-aspect-ratio morphologies not only play a significant role in providing mechanical reinforcement to the matrix but also enhance photo-actuation for both light driven volumetric contraction and expansion of spiropyran hydrogels. Molecular dynamics simulations indicate that water within the high-aspect-ratio supramolecular polymers exhibits a faster draining rate as compared to those in spherical micelles, which suggests that the high-aspect-ratio supramolecular polymers effectively facilitate the transport of trapped water molecules by functioning as channels and therefore enhancing actuation of the hybrid system. Our simulations provide a useful strategy for the design of new functional hybrid architectures and materials with the aim of accelerating response and enhancing actuation by facilitating water diffusion at the nanoscopic level.

2021

1. 

   Acrylic Paints: An Atomistic View of Polymer Structure and Effects of Environmental Pollutants

   Aysenur Iscen, Nancy C. Forero-Martinez, Omar Valsson, and 1 more author

   The Journal of Physical Chemistry B, Sep 2021

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2. 

   Advanced Materials for Energy-Water Systems: The Central Role of Water/Solid Interfaces in Adsorption, Reactivity, and Transport

   Edward Barry, Raelyn Burns, Wei Chen, and 37 more authors

   Chemical Reviews, Aug 2021

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2020

1. 

   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

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2. Supramolecular–covalent hybrid polymers for light-activated mechanical actuation

   Chuang Li, Aysenur Iscen, Hiroaki Sai, and 7 more authors

   Nature Materials, May 2020

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   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.

3. 

   Vibrational Probe of Aqueous Electrolytes: The Field Is Not Enough

   Nicholas H. C. Lewis, Aysenur Iscen, Alanna Felts, and 3 more authors

   The Journal of Physical Chemistry B, Aug 2020

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2019

1. 

   Inhibition of Amyloid-βAggregation by Cobalt(III) Schiff Base Complexes: A Computational and Experimental Approach

   Aysenur Iscen, Christopher R. Brue, Kaleigh F. Roberts, and 3 more authors

   Journal of the American Chemical Society, Oct 2019

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2. 

   Multivalent Cation-Induced Actuation of DNA-Mediated Colloidal Superlattices

   Devleena Samanta, Aysenur Iscen, Christine R. Laramy, and 4 more authors

   Journal of the American Chemical Society, Dec 2019

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3. 

   Hofmeister Effects on Peptide Amphiphile Nanofiber Self-Assembly

   Aysenur Iscen, and George C. Schatz

   The Journal of Physical Chemistry B, Aug 2019

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2018

1. 

   Highly Stable, Ultrasmall Polymer-Grafted Nanobins (usPGNs) with Stimuli-Responsive Capability

   Bong Jin Hong, Aysenur Iscen, Anthony J. Chipre, and 5 more authors

   The Journal of Physical Chemistry Letters, Mar 2018

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2017

1. Peptide amphiphile self-assembly

   Aysenur Iscen, and George C. Schatz

   EPL (Europhysics Letters), Aug 2017

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   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.