Alport Syndrome mutation changes molecular structure and nanomechanics of type IV tropocollagen

Maya Srinivasan, Sebastien G M Uzel, Alfonso Gautieri, Sinan Keten, Markus J. Buehler

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Alport Syndrome is a genetic disease characterized by the breakdown of the glomerular basement membrane (GBM) around blood vessels in the kidney, leading to kidney failure in most patients. It is the second most inherited kidney disease in the US, and many other symptoms are associated with the disease, including hearing loss and ocular lesions. Here we probe the molecular level mechanisms of this disease utilizing a bottom-up computational materiomics approach focused on the mutation associated with the most severe form of Alport Syndrome. Since the GBM is under constant mechanical loading due to blood flow, changes in mechanical properties due to amino acid mutations may be critical in the symptomatic GBM breakdown seen in Alport Syndrome patients. Through full-atomistic simulations in explicit solvent, the effects of a single-residue glycine substitution mutation are studied in a short segment of a collagen type IV tropocollagen molecule. Major changes are observed at the single molecule level of the mutated sequence, including a bent shape of the structures after equilibration with the kink located at the mutation site and a significant alteration of the molecule's stress-strain response and stiffness.

Original languageEnglish (US)
Title of host publicationStructure-Property Relationships in Biomineralized and Biomimetic Composites
PublisherMaterials Research Society
Pages17-22
Number of pages6
ISBN (Print)9781605111605
DOIs
StatePublished - 2009
Event2009 MRS Spring Meeting - San Francisco, CA, United States
Duration: Apr 14 2009Apr 17 2009

Publication series

NameMaterials Research Society Symposium Proceedings
Volume1187
ISSN (Print)0272-9172

Other

Other2009 MRS Spring Meeting
CountryUnited States
CitySan Francisco, CA
Period4/14/094/17/09

ASJC Scopus subject areas

  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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