Biophysical Society Thematic Meeting - October 25-30, 2015

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Polymers and Self Assembly: From Biology to Nanomaterials Poster Session I
36-POS Board 36
The Liquid Structure of Elastin Aggregates
Sarah Rauscher 1,2, Régis Pomès1,3.
1Hospital for Sick Children, Toronto, ON, Canada, 2Max Planck Institute for Biophysical
Chemistry, Goettingen, Germany, 3University of Toronto, Toronto, ON, Canada.
The protein elastin imparts extensibility, elastic recoil, and resilience to diverse tissues including
arterial walls, skin, lung alveoli, and the uterus. Elastin and elastin-like peptides are self-
aggregating polymers that undergo liquid-liquid phase separation upon increasing temperature
and are well-suited for biomaterials applications. Despite the biological importance of elastin and
decades of study, the structural and physico-chemical basis for the assembly and mechanical
properties of elastin has remained elusive. We provide an atomistic description of the structural
ensemble of an elastin-like aggregate using molecular dynamics simulations with a total time
exceeding 0.2 ms. The aggregate consists of highly-disordered chains that retain local secondary
structure in the form of hydrogen-bonded turns. The polypeptide backbone remains partly
hydrated as it is unable to form extensive secondary structure, precluding the formation of a
compact, solvent-excluding hydrophobic core. Consistent with the entropic nature of elastic
recoil, the aggregated state is stabilized both by the hydrophobic effect and by an increase in
conformational entropy upon self-assembly. These findings resolve the long-standing
controversy concerning the structure of elastin and reconcile seemingly contradictory features of
previous elastin models: it is because aggregated polypeptide chains form extensive
intermolecular interactions between non-polar groups that they approach the state in which their
chain entropy is maximized. The dramatic increase in conformational disorder upon aggregation
is consistent with the Flory theorem, which predicts maximal chain entropy for polymer chains
self-aggregating within a polymer melt. The fact that polypeptide chains can aggregate yet retain
functionally-essential conformational entropy is of broad relevance to the study of both protein
disorder and protein phase separation. The structural ensemble of the elastin-like aggregate
obtained here provides the first atomistic view into what may be described as the liquid state of
proteins.