Liquid to solid transition of elastin condensates

Ceballos, Alfredo Vidal; Preston, John; Vairamon, Christo; Shen, Christopher; Koder, Ronald L.; Elbaum‐Garfinkle, Shana

doi:10.1073/pnas.2202240119

Cited by 21 publications

(12 citation statements)

References 57 publications

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“…The domains within mini-elastin are often simplified versions of the natural domains, that is, they are regular repeats of a given sequence motif. Despite being a synthetic and simplified versions of elastin, the mini-elastins are excellent models for studying elastin-related processes (Keeley et al, 2002; Bellingham et al, 2003; Vidal Ceballos et al, 2022).…”

Section: Definitionsmentioning

confidence: 99%

“…This phenomenon is remarkably important when the elastin coacervate is considered as elastin chains are extremely dynamics. Nevertheless, results obtained on the molecular basis for phase separation of hydrophobic elastin-like domains, block copolymer peptides mimicking alternating hydrophobic and cross-linking domains, or mini-elastin provide important insights into the structural and physicochemical basis for the elasticity of elastin (Rauscher and Pomès, 2017; Reichheld et al, 2017; Vidal Ceballos et al, 2022).…”

Section: Elasticitymentioning

confidence: 99%

“…Recently, a mini-elastin mimicking the alternating domain structure of tropoelastin was used to examine the coacervation process of elastin in the absence of exogenous cross-links (Vidal Ceballos et al, 2022). Using differential interference contrast, fluorescence and particle-tracking micro-rheology, the transitions occurring in mini-elastin revealed that the liquid transition presents an intermediate step where randomly distributed insoluble materials (i.e.…”

Section: Elasticitymentioning

confidence: 99%

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Structural and physical basis for the elasticity of elastin

Depenveiller,

Baud,

Belloy

et al. 2024

Quart. Rev. Biophys.

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Elastin function is to endow vertebrate tissues with elasticity so that they can adapt to local mechanical constraints. The hydrophobicity and insolubility of the mature elastin polymer have hampered studies of its molecular organisation and structure-elasticity relationships. Nevertheless, a growing number of studies from a broad range of disciplines have provided invaluable insights, and several structural models of elastin have been proposed. However, many questions remain regarding how the primary sequence of elastin (and the soluble precursor tropoelastin) governs the molecular structure, its organisation into a polymeric network, and the mechanical properties of the resulting material. The elasticity of elastin is known to be largely entropic in origin, a property that is understood to arise from both its disordered molecular structure and its hydrophobic character. Despite a high degree of hydrophobicity, elastin does not form compact, water-excluding domains and remains highly disordered. However, elastin contains both stable and labile secondary structure elements. Current models of elastin structure and function are drawn from data collected on tropoelastin and on elastin-like peptides (ELPs) but at the tissue level, elasticity is only achieved after polymerisation of the mature elastin. In tissues, the reticulation of tropoelastin chains in water defines the polymer elastin that bears elasticity. Similarly, ELPs require polymerisation to become elastic. There is considerable interest in elastin especially in the biomaterials and cosmetic fields where ELPs are widely used. This review aims to provide an up-to-date survey of/perspective on current knowledge about the interplay between elastin structure, solvation, and entropic elasticity.

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Section: Definitionsmentioning

confidence: 99%

Section: Elasticitymentioning

confidence: 99%

Section: Elasticitymentioning

confidence: 99%

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Structural and physical basis for the elasticity of elastin

Depenveiller,

Baud,

Belloy

et al. 2024

Quart. Rev. Biophys.

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“…The elastic matrix is formed when tropoelastin, one of the most hydrophobic proteins found in nature, is exported to the extracellular matrix and undergoes a liquid-liquid phase separation followed by enzymatic cross-linking (17, 18). Tropoelastin is organized in alternating proline-rich hydrophobic domains and alanine-rich crosslinking domains.…”

Section: Introductionmentioning

confidence: 99%

Elastin Recoil is Driven by the Hydrophobic Effect

Jamhawi

Koder

Wittebort

2023

Preprint

Self Cite

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Elastin is an extracellular matrix material formed when the precursor protein, tropoelastin, undergoes coacervation and crosslinking. It is found in all vertebrates where its reversible elasticity, robustness and low stiffness are essential for the normal function of arteries, lungs, and skin. It is among the most resilient elastic materials known: During a human lifetime, arterial elastin undergoes in excess of 109stretching/contracting cycles without being replaced or repaired and its slow oxidative hardening has been identified as one of the hard limits on human lifespan. The physical basis for these properties, most notably the molecular mechanism of entropic recoil, have been a source of controversy for over fifty years. Herein, we report a combined NMR and thermomechanical study of elastin that establishes the hydrophobic effect as the primary driver of elastin function. Water ordering at the solvent:protein interface was directly observed as a function of stretch at the molecular level using double quantum filtered 2H NMR and the most extensive thermodynamic analysis of elastin function performed to date was obtained by measuring elastin length and volume as a function of applied force and temperature in normal water, heavy water and with added co-solvents. When elastin is stretched, the heat capacity increases, water is ordered proportional to the degree of stretching, elastin′s internal energy decreases, and heat is released in excess of the work performed. Together, these properties show that spontaneous recoil in elastin at physiological temperatures and conditions is primarily driven by the hydrophobic effect. Consistent with this conclusion are decreases in the thermodynamic signatures when co-solvents that alter the hydrophobic effect are introduced. Hydrophobic effect-driven recoil, as opposed to a configurational entropy mechanism where hardening from crystallization can occur, may be the origin of elastin′s unusual resilience.

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“…These numerical studies are in accord with the recent experimen-tal work, which reports the formation of transient β -turns in highly dynamic hydrophobic domains resolved by NMR spectroscopy 27 . However, Ceballos and coworkers demonstrated experimentally that the aggregate state of elastin condensates can depend on the length of its hydrophobic domains, where the transition from liquid-like droplets to more solid-like occurs with increasing chain length of hydrophobic domains 28 . This work highlighted the importance of the chain length as a modulator of the material state of elastin condensates.…”

mentioning

confidence: 99%

Sequence length controls coil-to-globule transition in elastin-like polypeptides

Morozova,

García,

Barrat

2023

Preprint

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Phase separation of disordered proteins resulting in the formation of biocondensates has received significant attention due to its fundamental role in cellular organization and functioning and is sought after in many applications. For instance, the liquid-liquid phase separation of tropoelastin initiates the hierarchical assembly process of elastic fibers, which are key components of the extracellular matrix providing resilience and elasticity to biological tissues. Inspired by the hydrophobic domains of tropoelastin, elastin-like polypeptides (ELPs) were derived which exhibit a similar phase behavior. Even though, it appeared almost certain that elastin condensates retain liquid-like properties, a recent experimental study questioned this viewpoint by demonstrating that the aggregate state of elastin-derived materials can depend on the length of hydrophobic domains. Here, we employ state-of-the-art atomistic modeling to resolve the conformational ensembles of a single ELP as a function of its sequence length in the temperature range relevant to possible applications. For the first time, we report the free energy profiles of ELPs in the vicinity of conformational transitions which show more compact polypeptide conformations at higher temperatures in accord with their thermoresponsive nature. We access the conformations visited by ELPs through descriptors from polymer physics. We find that short ELPs always remain in coil-like conformations, while the longer ones prefer globule states. The former engages in intrapeptide hydrogen bonds temporarily retaining their liquid-like properties while the latter forms long-lived (hundreds of nanoseconds) intra-peptide hydrogen bonds attributed to ordered secondary structure motifs such asβ-bridges and turns. Our work demonstrates the importance of the sequence length as a modulator of conformational properties at a single chain and possibly explains the change in aggregate state in elastin condensates.

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Liquid to solid transition of elastin condensates

Cited by 21 publications

References 57 publications

Structural and physical basis for the elasticity of elastin

Structural and physical basis for the elasticity of elastin

Elastin Recoil is Driven by the Hydrophobic Effect

Sequence length controls coil-to-globule transition in elastin-like polypeptides

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