Sequence‐Tunable Phase Behavior and Intrinsic Fluorescence in Dynamically Interacting Peptides

Sementa, Deborah; Dave, Dhwanit; Fisher, Rachel S.; Wang, Tong; Elbaum‐Garfinkle, Shana; Ulijn, Rein V.

doi:10.1002/anie.202311479

Cited by 13 publications

(2 citation statements)

References 55 publications

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“…The details of each system are summarized in Table S2. The number of hydrogen bonds, proximal radial distribution functions (pRDF), (49,50) solvent accessible surface area (SASA), and the number of π-π and cation-π interaction pairs were calculated using the combination of the last 300 ns of the three replicates.…”

Section: Molecular Dynamics (Md) Simulationsmentioning

confidence: 99%

Phase-Separating Peptide Coacervates with Programmable Material Properties for Universal Intracellular Delivery of Macromolecules

Sun,

Wu,

et al. 2024

Preprint

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Phase-separating peptides (PSPs) self-assembling into coacervate microdroplets (CMs) are a promising new class of intracellular delivery vehicles that can release macromolecular modalities deployed in a wide range of therapeutic treatments. However, the molecular grammar governing intracellular uptake and release kinetics of CMs remains elusive. Here, we systematically manipulated the sequence of PSPs to unravel the relationships between their molecular structure, the physical properties of the resulting CMs, and their delivery efficacy. We show that a few amino acid alterations are sufficient to modulate the viscoelastic properties of CMs towards either a gel-like or a liquid-like state as well as their binding interaction with cellular membranes, collectively enabling to tune the kinetics of intracellular cargo release. Our findings provide molecular guidelines to precisely program the material properties of PSP CMs and achieve tunable cellular uptake and release kinetics depending on the cargo modality, with broad implications for therapeutic applications.

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Section: Molecular Dynamics (Md) Simulationsmentioning

confidence: 99%

Phase-Separating Peptide Coacervates with Programmable Material Properties for Universal Intracellular Delivery of Macromolecules

Sun,

Wu,

et al. 2024

Preprint

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“…The dipeptide FF-OMe (C-terminal methoxylated diphenylalanine) also shows LLPS upon increase of pH, as do related methoxylated tripeptides FFG-OMe and FFE-OMe . In another recent example, LLPS was demonstrated for short arginine- or histidine-containing 22-residue peptides with IDP-like spacers (repeat GLG sequences) …”

Section: Introductionmentioning

confidence: 99%

Minimal Peptide Sequences That Undergo Liquid–Liquid Phase Separation via Self-Coacervation or Complex Coacervation with ATP

Castelletto,

Seitsonen,

Pollitt

et al. 2024

Biomacromolecules

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The simple (self-)coacervation of the minimal tryptophan/arginine peptide sequences W2R2 and W3R3 was observed in salt-free aqueous solution. The phase diagrams were mapped using turbidimetry and optical microscopy, and the coacervate droplets were imaged using confocal microscopy complemented by cryo-TEM to image smaller droplets. The droplet size distribution and stability were probed using dynamic light scattering, and the droplet surface potential was obtained from zeta potential measurements. SAXS was used to elucidate the structure within the coacervate droplets, and circular dichroism spectroscopy was used to probe the conformation of the peptides, a characteristic signature for cation−π interactions being present under conditions of coacervation. These observations were rationalized using a simple model for the Rayleigh stability of charged coacervate droplets, along with atomistic molecular dynamics simulations which provide insight into stabilizing π–π stacking interactions of tryptophan as well as arginine–tryptophan cation−π interactions (which modulate the charge of the tryptophan π-electron system). Remarkably, the dipeptide WR did not show simple coacervation under the conditions examined, but complex coacervation was observed in mixtures with ATP (adenosine triphosphate). The electrostatically stabilized coacervation in this case provides a minimal model for peptide/nucleotide membraneless organelle formation. These are among the simplest model peptide systems observed to date able to undergo either simple or complex coacervation and are of future interest as protocell systems.

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General and Versatile Nanoarchitectonics for Amino Acid‐Based Glasses via Co‐Assembly of Organic Counterions

Li,

Yang,

Zhao

et al. 2024

Angewandte Chemie

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Amino acid‐based biomolecular glasses represent an emerging material to meet the demand for sustainable development. However, most amino acids are difficult to vitrify due to their strong crystallization tendency, limiting further advancements of this field. In this study, we demonstrate that the introduction of counterions effectively suppresses crystallization, as hydrogen bonds within the system stabilize the disordered structures. Based on this, we propose a counterion co‐assembly strategy to synthesize a wide range of amino acid‐based glasses. This strategy enables the facile fabrication of glass with customizable shapes, high mechanical rigidity, and tunable multicolor fluorescence, ranging from blue to red depending on the excitation wavelength. Furthermore, this strategy allows the integration and enhancement of counterion properties within the glass matrix. Through the co‐assembly of phosphorescent counterions, we synthesized a series of long‐persistent luminescent glasses with significantly extended afterglow lifetimes. This work presents an effective approach for the synthesis of amino acid‐based glasses and provides insights into the development of supramolecular glasses with tailored functionalities.

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Sequence‐Tunable Phase Behavior and Intrinsic Fluorescence in Dynamically Interacting Peptides

Cited by 13 publications

References 55 publications

Phase-Separating Peptide Coacervates with Programmable Material Properties for Universal Intracellular Delivery of Macromolecules

Phase-Separating Peptide Coacervates with Programmable Material Properties for Universal Intracellular Delivery of Macromolecules

Minimal Peptide Sequences That Undergo Liquid–Liquid Phase Separation via Self-Coacervation or Complex Coacervation with ATP

General and Versatile Nanoarchitectonics for Amino Acid‐Based Glasses via Co‐Assembly of Organic Counterions

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