Computational Investigations of Cellular Functions: Three Cases on Membrane Morphogenesis, Organization and Assembly of a Multi-Protein Complex, and the Molecular Origin of Muscle Elasticity

Titin is a mechanical protein that protects muscle from overstretching by producing a restoring force when a muscle fiber is extended beyond its normal length. Force spectroscopy studies have shown that titin exhibits several regimes of elasticity. Disordered segments bring about a soft, entropic spring-type elasticity; secondary structures of titins immunoglobulin-like (Ig-) and fibronectin type III-like (FN-III) domains provide a stiff elasticity. We demonstrated that titin exhibits a third type of elasticity due to tertiary structure and involving domain-domain interaction and reorganization along the titin chain. Through simulations employing equilibrium molecular dynamics, steered molecular dynamics, and free-energy calculations, the mechanical properties of a six-Ig domain of titin (I65-I70), for which a crystallographic structure is available, were investigated. The results reveal a soft tertiary structure elasticity. A remarkably accurate statistical mechanical description for this elasticity is derived and applied. Simulations studied also the stiff, secondary structure elasticity of the I65-I70 chain due to the unraveling of its domains and revealed how force propagates along the chain during the secondary structure elasticity response.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Physics

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Hsin, Ya-Chieh

Contributors dc:contributor

• Aksimentiev, Aleksei
• Schulten, Klaus

• Biology, Cell

Language dc:language

eng

Identifier

(MiAaPQ)AAI3452176

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/80632