A Coarse-Grained Molecular Dynamics model of the Mammalian Nuclear Envelope
Open Access
- Author:
- Singh, Pranjal
- Graduate Program:
- Engineering Science and Mechanics
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- June 29, 2021
- Committee Members:
- Sulin Zhang, Thesis Advisor/Co-Advisor
Francesco Costanzo, Committee Member
Albert Segall, Program Head/Chair
Christian Peco, Committee Member
Judith Todd Copley, Committee Member - Keywords:
- nuclear envelope
nuclear lamina
coarse-grained modeling
molecular dynamics
viscoelasticity - Abstract:
- The cell nucleus houses most of the genetic material in eukaryotic cells and is the site of many fundamental genome regulatory processes including cell division, gene expression, differentiation, and aging. The regulation of architecture of the nuclear envelope (NE) is essential for smooth operation of these processes. There is currently no physics-based model, theoretical or computational, which accounts for all significant interactions of subnuclear components in a common framework, leaving much of NE mechanics unexplored and poorly understood. We present a coarse-grained molecular dynamics model of the mammalian NE of unprecedented detail. A three-step protocol is shown to generate a coarse-grained nuclear envelope (CGNE) with experimentally consistent structure. The CGNE features a monolayer model of the nuclear membranes and a dynamically-linked meshwork model of the underlying nuclear lamina. Peripheral chromatin, which supports the meshwork from underneath and also interlaces with it, is modeled as a chain of mesoscale domains. The methodologies for in silico mechanical testing of the CGNE and extraction of metrics of NE viscoelasticity from the simulation data are described. Parameters are being tuned towards achieving experimental consistency of these viscoelastic properties. A revised CGNE model is planned to be published elsewhere in the near future.