title: Modeling the Excess Cell Surface Stored in a Complex Morphology of Bleb-Like Protrusions.
abstract: Cells transition from spread to rounded morphologies in diverse physiological contexts including mitosis and mesenchymal-to-amoeboid transitions. When these drastic shape changes occur rapidly, cell volume and surface area are approximately conserved. Consequently, the rounded cells are suddenly presented with a several-fold excess of cell surface whose area far exceeds that of a smooth sphere enclosing the cell volume. This excess is stored in a population of bleb-like protrusions (BLiPs), whose size distribution is shown by electron micrographs to be skewed. We introduce three complementary models of rounded cell morphologies with a prescribed excess surface area. A 2D Hamiltonian model provides a mechanistic description of how discrete attachment points between the cell surface and cortex together with surface bending energy can generate a morphology that satisfies a prescribed excess area and BLiP number density. A 3D random seed-and-growth model simulates efficient packing of BLiPs over a primary rounded shape, demonstrating a pathway for skewed BLiP size distributions that recapitulate 3D morphologies. Finally, a phase field model (2D and 3D) posits energy-based constitutive laws for the cell membrane, nematic F-actin cortex, interior cytosol, and external aqueous medium. The cell surface is equipped with a spontaneous curvature function, a proxy for the cell surface-cortex couple, that is a priori unknown, which the model "learns" from the thin section transmission electron micrograph image (2D) or the "seed and growth" model image (3D). Converged phase field simulations predict self-consistent amplitudes and spatial localization of pressure and stress throughout the cell for any posited stationary morphology target and cell compartment constitutive properties. The models form a general framework for future studies of cell morphological dynamics in a variety of biological contexts.
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Maryna
authors.initials: M
authors.lastname: Kapustina
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States of America.|Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Denis
authors.initials: D
authors.lastname: Tsygankov
authors.affiliation: Department of Mathematics, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Mathematics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wessler
authors.affiliation: Department of Mathematics, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Mathematics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Alex
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Nathan
authors.initials: N
authors.lastname: Roach
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Elston
authors.affiliation: Department of Mathematics, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.|Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Ken
authors.initials: K
authors.lastname: Jacobson
authors.affiliation: Department of Mathematics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|Departments of Applied Physical Sciences and Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: M Gregory
authors.initials: MG
authors.lastname: Forest
mesh_terms: D000818:Animals; D016466:CHO Cells; D048429:Cell Size; D022081:Cell Surface Extensions / Q000737:chemistry* / Q000648:ultrastructure*; D003198:Computer Simulation; D003412:Cricetulus; D008560:Membrane Fluidity; D008956:Models, Chemical; D008958:Models, Molecular