Traumatic brain injury (TBI) is an injury that results from an application of a shear mechanical force to the head and causes different types of damages to the brain. The TBIs outcomes at the cellular level are mechanical breaking of axonal cytoskeleton, transport interruption and swelling. To elucidate better what happens during the injury at the cellular and molecular level, it is important to understand what happens when mechanical stress is applied to the axon, the long and slender projection of a nerve cell. With a proper understanding of the cellular and molecular mechanisms following trauma to the human brain, better protective systems such as helmets as well as candidates for therapeutic drugs against brain injuries can be developed. In the current project we will focus on how external factors such as stress and strain affect the axon's plasma membrane and the myelin sheath (a sheath surrounding the axon of some nerves) at the microscopic level. To address this, we use classical molecular dynamics (MD) simulations to provide a three-dimensional description of the membrane system.
Our recent results have shown that lipid compositions play a key role in membrane structure-mechanical properties. In particular, galactosylceceramides (present mainly in myelin sheath) makes the membrane more resilient to extension and to water penetration (Saeedimasine et al. manuscript in progress). Now we want to move on and use lipid bilayers that account for variegate composition of plasma membranes and myelin sheaths. We will simulate the bilayers in presence and in absence of membrane proteins. To mimic the effect of the mechanical stress on the membranes simulations we will stretch the lipid bilayer in x and y dimensions at different speeds and/or applying different pressure load to perpendicular to membrane plane.
Simulations in the order of milliseconds will be needed to account for the
time scale of the TBI (e.i impact in the injury will evolve in the order of ms). To achieve this, we will combine classical mechanics with coarse-grained models. The obtained results will be also coupled with the finite element description of the axon fiber, developed by the group of Svein Kleiven (KTH).