UNCOVERING FUNDAMENTAL MECHANISMS OF ACTOMYOSIN CONTRACTILITY USING ANALYTICAL THEORY AND COMPUTER SIMULATION

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dc.contributor.advisorPapoian, Garegin Aen_US
dc.contributor.authorKomianos, James Ericen_US
dc.contributor.departmentBiophysics (BIPH)en_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2018-09-07T05:42:34Z
dc.date.available2018-09-07T05:42:34Z
dc.date.issued2018en_US
dc.description.abstractActomyosin contractility is a ubiquitous force-generating function of almost all eukaryotic organisms. While more understanding of its dynamic non-equilibrium be- havior has been uncovered in recent years, little is known regarding its self-emergent structures and phase transitions that are observed in vivo. With this in mind, this thesis aims to develop a state-of-the-art computational model for the simulation of actomyosin assemblies, containing detailed cytosolic reaction-diffusion processes such as actin filament treadmilling, cross-linker (un)binding, and molecular motor walking. This is explicitly coupled with novel mechanical potentials for semi-flexible actin filaments. Then, using this simulation framework combined with other ana- lytical approaches, we propose a novel mechanism of contractility in a fundamental actomyosin structural element, derived from a thermodynamic free energy gradi- ent favoring overlapped actin filament states when passive cross-linkers are present. With this spontaneous cross-linking, transient motors such as non-muscle myosin II can generate robust network contractility in a collective myosin II-cross-linker ratcheting mechanism. Finally, we map the phases of contractile behavior of disor- dered actomyosin using this theory, showing explicitly the cross-linking, motor and boundary conditions required for geometric collapse or tension generation in a net- work comprised of those elements. In this theory, we move away from the sarcomeric contractility mechanism typically reconciled in disordered non-muscle structures. It is our hope that this study adds theoretical knowledge as well as computational tools to study the diverse contractile assemblies found in non-muscle actomyosin networks.en_US
dc.identifierhttps://doi.org/10.13016/M2NG4GW0B
dc.identifier.urihttp://hdl.handle.net/1903/21163
dc.language.isoenen_US
dc.subject.pqcontrolledBiophysicsen_US
dc.subject.pqcontrolledApplied physicsen_US
dc.subject.pqcontrolledThermodynamicsen_US
dc.subject.pquncontrolledActomyosinen_US
dc.subject.pquncontrolledComplex networksen_US
dc.subject.pquncontrolledComputer simulationen_US
dc.subject.pquncontrolledContractilityen_US
dc.subject.pquncontrolledFree energyen_US
dc.subject.pquncontrolledStochastic modelingen_US
dc.titleUNCOVERING FUNDAMENTAL MECHANISMS OF ACTOMYOSIN CONTRACTILITY USING ANALYTICAL THEORY AND COMPUTER SIMULATIONen_US
dc.typeDissertationen_US

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