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Open Access Publications from the University of California

Actin filaments and networks under force: A computational study

  • Author(s): Wang, Evan Bo
  • Advisor(s): Geissler, Phillip
  • et al.
Abstract

Rich understanding of a complex system can often emerge from simple but carefully constructed models. With an appropriate model, we can ask questions about how tuning the parameters of the model or modifying the constraints of the system changes the system behavior. My research involves applying such an approach to actin, an essential biopolymer in the cell. In this work, we explore how forces affect actin at the filament and network length scales.

In the first part, we investigate how different forces modulate the interaction between actin filaments and actin-binding proteins. One such protein complex, Arp2/3, can cause filaments to form branches. Experiments indicate that branches preferentially form on the convex side of bent filaments. Using a coarse-grained model discretized at the monomer pair level, we show that binding is dependent upon a high local curvature fluctuation of the filament. The results indicate that actin can sense and respond to mechanical environmental cues to regulate the binding of Arp2/3. We further believe such a picture can serve as a useful framework for studying the effects of force on the binding and function of other proteins. In a follow-up project, we derive analytical expressions for the nanoscale curvature distribution of a worm-like chain and membrane as a function of applied tension. These expressions can be used to understand the force dependence of protein binding on actin filaments and membranes within a biological context.

In the second part, we focus on actin network elasticity. Specifically, we explore how actin networks respond to large external forces. However, the theoretical toolkit for such a task is incomplete. First we develop a constant-stress framework to apply large forces on soft but strongly nonlinear materials. Additionally, we create a toy model of a soft elastic solid with a nonlinear elastic response on which we test our constant-stress method. Finally, we utilize the constant-stress method and a coarse-grained model for short, semiflexible chains to explore actin network elasticity under compression. We consistently observe stress softening under compression, which we analyze from a single filament perspective and using normal mode analysis.

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