Theoretical analysis of the effect of the transbilayer movement of phospholipid molecules on the dynamic behavior of a microtube pulled out of an aspirated vesicle.

Observations over extended times of a lipid microtube (tether) formed from a lecithin vesicle have shown that under constant external loads the tether exhibits a continuous slow growth. It is considered that this growth is a consequence of the net transbilayer movement of phospholipid molecules in a direction which relieves the membrane strain resulting from the elastic deformation of the vesicle. The elastic deformation mode responsible for this effect is identified as the relative expansion of the two membrane layers reflecting the non-local contribution to membrane bending. An equation for the consequent rate of transbilayer movement of phospholipid molecules is derived. The dynamic behavior of the system is modeled by including frictional contributions due to interlayer slip and Stokes drag on the glass bead used to form the tether. The general numerical solution reveals a complex dependence of the tether growth rate on the system parameters and a continuous increase in the rate of tether growth at long times. Closed form expressions approximating the system behavior are derived and the conditions under which they can be applied are specified. Modeling the mechanically-driven lipid transport as a simple, stochastic, thermal process, allows the rate of lipid translocation to be related to the equilibrium transbilayer exchange rate of phospholipid molecules. Consideration of experimental results shows that the time constant for mechanically-driven translocation is shorter than the time for diffusion-driven translocation by approximately two orders of magnitude, indicating that lipid translocation is not a simple diffusive process.