The liquid structure of elastin

Abstract

The protein elastin imparts extensibility, elastic recoil, and resilience to tissues including arterial walls, skin, lung alveoli, and the uterus. Elastin and elastin-like peptides are hydrophobic, disordered, and undergo liquid-liquid phase separation upon self-assembly. Despite extensive study, the structure of elastin remains controversial. We use molecular dynamics simulations on a massive scale to elucidate the structural ensemble of aggregated elastin-like peptides. Consistent with the entropic nature of elastic recoil, the aggregated state is stabilized by the hydrophobic effect. However, self-assembly does not entail formation of a hydrophobic core. The polypeptide backbone forms transient, sparse hydrogen-bonded turns and remains significantly hydrated even as self-assembly triples the extent of non-polar side chain contacts. Individual chains in the assembly approach a maximally-disordered, melt-like state which may be called the liquid state of proteins. These findings resolve long-standing controversies regarding elastin structure and function and afford insight into the phase separation of disordered proteins.

Protein Phase Separation: A New Phase in Cell Biology

“…Compellingly, these recent findings are already opening novel avenues to target aberrant protein phase transitions in human disease. Additionally, understanding the relationship between sequence and the resulting material state may also lead to novel synthetic biomaterials [140,141]. …”

Pressure‐Induced Dissolution and Reentrant Formation of Condensed, Liquid–Liquid Phase‐Separated Elastomeric α‐Elastin

“…[7] The in-tensityo ft his band decreases with increasing temperature and shifts to larger wavenumbers, and ab road band appears at 1650 cm À1 ,w hich is characteristico fm ore loop/turn (or,l ess likely, a-helical) structures. [7][8][9] To corroborate the FT-IR data, circular dichroism (CD) spectra were also recorded. [7] The band that appears at~1614 cm À1 is probablyd ue to the IR absorption of terminal COO À groups.…”

Engineering the Architecture of Elastin‐Like Polypeptides: From Unimers to Hierarchical Self‐Assembly

“…A unique feature of ELP polymers that is useful for therapeutic applications is their LCST phase behavior, which allows stimulus‐triggered assembly or disassembly . This LCST behavior is intricately tied to the ELP molecular structure—or more accurately, the lack thereof . Chilkoti—and others—have argued that ELPs represent a near‐ideal elastomeric disordered protein, and that the molecular malleability afforded by this disorder is a critical component of the thermodynamic origin of the polymer's phase behavior .…”

“…[43,[98][99][100] This LCST behavior is intricately tied to the ELP molecular structure-or more accurately, the lack thereof. [101] Chilkoti-and others-have argued that ELPs represent a near-ideal elastomeric disordered protein, [102][103][104] and that the molecular malleability afforded by this disorder is a critical component of the thermodynamic origin of the polymer's phase behavior. [101,105,106] Though critical for stimuli-responsive behavior, the structural disorder of ELPs limits the structural complexity available after aggregation.…”

“…[101] Chilkoti-and others-have argued that ELPs represent a near-ideal elastomeric disordered protein, [102][103][104] and that the molecular malleability afforded by this disorder is a critical component of the thermodynamic origin of the polymer's phase behavior. [101,105,106] Though critical for stimuli-responsive behavior, the structural disorder of ELPs limits the structural complexity available after aggregation. ELPs alone are largely constrained to the formation of micelles or microscale liquid-like coacervates with no internal architecture.…”