Dynamic Failure of a Lamina Meshwork in Cell Nuclei under Extreme Mechanical Deformation

Abstract

The nuclear lamina is a structural protein meshwork at the inner nuclear membrane. It confers mechanical strength to the cell's nucleus and also sustains the overall structural integrity of the cell. The rupture of nuclear lamina is involved in many physiologically extreme conditions, such as cell division, genetic disease, and injury. Yet, its rupture mechanisms and processes are largely unknown and failure models commonly used for engineering materials cannot be directly applied due to the complex hierarchical structure. Here, we use a multiscale modeling technique to investigate the dynamic failure of the nuclear lamina meshwork from the bottom up. We find that flaws or cracks in the nuclear lamina act as seeds for catastrophic failure that propagate rapidly upon very large deformation. Fracture occurs via crack propagation at intersonic speeds, and greater than the Rayleigh-wave speed predicted as a limit by classical fracture theory but smaller than the longitudinal wave speed. Our analysis shows that nanoscale secondary structural changes in protein filaments such as the alpha-beta transition and intermolecular sliding explain this macroscale phenomenon. Based on a simple model, we discover that the crack propagation speed is governed by the square root of the ratio of the tangent material moduli in (E x ) and perpendicular (E y ) to the crack propagationwhere the relative levels of applied strains in the x-and y-direction control the crack speed.

Mechanics of Microtubules from a Coarse-Grained Model

“…A reasonable model to investigate the cellular level activities of MTs is expected by utilizing a coarse-grain model starting from the tubulin monomers as building blocks. Similar studies have been reported for collagen and IFs networks [44,53,54]. Here in this work, we will investigate mechanics and dynamics of MTs at experimentally comparable length and time scales following this line.…”

“…The model is used to directly predict thermodynamic and mechanical properties of MTs after being validated by available experimental results, as summarized in Table 2. In combination with other coarsegrained models for AFs, IFs, etc., to establish a robust model at whole-cell level [53,54,65].…”