Biophysical Society Thematic Meeting - October 25-30, 2015

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 Pomès 1,3 . 1 Hospital for Sick Children, Toronto, ON, Canada, 2 Max Planck Institute for Biophysical Chemistry, Goettingen, Germany, 3 University 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.

- 60 -