A mechanical model for cytoskeleton and membrane interactions in neuronal growth cones

Revealing the molecular events of neuronal growth is critical to obtaining a deeper understanding of nervous system development, neural injury response, and neural tissue engineering. Central to this is the need to understand the mechanical interactions among the cytoskeleton and the cell membrane, and how these interactions affect the overall growth mechanics of neurons. Using ANSYS, the force produced by a cytoskeletal protein acting against a deformable membrane was modeled, and the deformation, stress, and strain were computed for the membrane. Parameters to represent the flexural rigidities of the well-studied actin and tubulin cytoskeletal proteins as well as the mechanical properties of neuronal growth cones were used in the simulations. Our model predicts that while a single actin filament is able to produce a force sufficient to cause membrane deformation and thus growth, it is also possible that the actin filament may cause the membrane to rupture, if a dilatational strain of more than 3-4% occurs. Additionally, neurotoxins or pharmaceuticals that alter the mechanical properties of either the cell membrane or cytoskeletal proteins could disrupt the balance of forces required for neurons to not only push out and grow correctly, but also to sustain their shapes as high-aspect-ratio structures once growth is complete. Understanding how cytoskeletal elements have coevolved mechanically with their respective cell membranes will yield insights into the events that gave rise to the sequences and quaternary structures of the major cytoskeletal elements.