Role of combined cell membrane and wall mechanical properties regulated by polarity signals in cell budding.

Budding yeast, Saccharomyces cerevisiae, serves as a prime biological model to study mechanisms underlying asymmetric growth. Previous studies have shown that prior to bud emergence, polarization of a conserved small GTPase Cdc42 must be established on the cell membrane of a budding yeast. Additionally, such polarization contributes to the delivery of cell wall remodeling enzymes and hydrolase from cytosol through the membrane, to change the mechanical properties of the cell wall. This leads to the hypothesis that Cdc42 and its associated proteins at least indirectly regulate cell surface mechanical properties. However, how the surface mechanical properties in the emerging bud are changed and whether such change is important are not well understood. To test several hypothesised mechanisms, a novel three-dimensional coarse-grained particle-based model has been developed which describes inhomogeneous mechanical properties of the cell surface. Model simulations predict alternation of the levels of stretching and bending stiffness of the cell surface in the bud region by the polarized Cdc42 signals is essential for initiating bud formation. Model simulations also suggest that bud shape depends strongly on the distribution of the polarized signaling molecules while the neck width of the emerging bud is strongly impacted by the mechanical properties of the chitin and septin rings. Moreover, the temporal change of the bud mechanical properties is shown to affect the symmetry of the bud shape. The 3D model of asymmetric cell growth can also be used for studying viral budding and other vegetative reproduction processes performed via budding, as well as detailed studies of cell growth.