Role of combined cell membrane and wall mechanical properties regulated by polarity signals in cell budding Kevin Tsai 1,2 , Samuel Britton 1,2 , Ali Nematbakhsh 1,2,3 , Roya Zandi 4,2 , Weitao Chen 1,2, *, Mark Alber 1,2, * 1 Department of Mathematics, University of California, Riverside, CA 2 Interdisciplinary Center for Quantitative Modeling in Biology, University of California, Riverside, CA 3 Department of Biochemistry and Molecular Biology, Penn State University, PA 4 Department of Physics, University of California, Riverside, CA * authors for correspondence: Mark Alber, malber@ucr.edu; Weitao Chen, weitaoc@ucr.edu Keywords: yeast, budding, asymmetric cell growth, multi-scale, three-dimensional modeling, particle model, protein polarization, visco-elastic Abstract The budding yeast, Saccharomyces cerevisiae, is a prime biological model to study mechanisms underlying asymmetric growth. Previous studies have shown that, prior to yeast bud emergence, polarization of a conserved small GTPase, Cdc42, must be established. Additionally, hydrolase changes the mechanical properties of the cell wall and plasma membrane with the periplasm between them (cell surface). However, how the surface mechanical properties in the emerging bud are different from the properties of the mother cell and their role in bud formation are not well understood. We hypothesize that the polarized chemical signal alters the local dimensionless ratio of stretching to bending stiffness of the cell surface of the emerging yeast bud. To test this hypothesis, a novel three-dimensional coarse-grained particle-based model has been developed which describes inhomogeneous mechanical properties of the cell surface. Model simulations suggest that regulation of the dimensionless ratio of stretching to bending stiffness of the cell surface is necessary to initiate bud formation. Furthermore, model simulations predict that bud shape depends strongly on the experimentally observed molecular distribution of the polarized signaling molecule Cdc42, while the neck shape of the emerging bud is strongly impacted by the properties of the chitin and septin ring. This 3D model of asymmetric cell growth can also be used for studying viral budding and other vegetative reproduction processes performed via budding. was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which this version posted May 1, 2020. ; https://doi.org/10.1101/2020.04.30.071456 doi: bioRxiv preprint