Theoretical modeling is a natural partner of cell and molecular biology. This synergy was illustrated during the Minisymposium on Modeling and Simulation of Cellular Functions, which presented a variety of theoretical approaches to cell biology problems. The topics discussed spanned various biological scales, from the organization of intracellular components to cell shape mechanics and gene expression studies. Computational simulation-based models, as well as analytical approaches in which coarse-grained equations with a limited number of parameters are directly solved, were presented. Importantly, the various modeling approaches were developed in close connection with experiments, highlighting how quantitative cross-talk between theory and experiments can be instrumental in addressing crucial biological questions. Anand Banerjee (National Institutes of Health) presented a kinetic model of clathrin-coated pit formation. Using Monte Carlo simulations, he could predict a lifetime distribution of abortive pits in striking agreement with lifetime distributions experimentally measured in total internal reflection fluorescence experiments. Moreover, changes in the physical parameters underlying the model upon cargo binding could facilitate clathrin vesicle formation by decreasing the associated energy barrier. Justin Bois (University of California, Los Angeles) investigated the polarization of the single-cell Caenorhabditis elegans embryo, in which membrane-associated polarity determinants (PAR proteins) are positioned to their respective poles of the cell concurrent with a concerted flow of the actomyosin cortex. Using a coarse-grained hydrodynamic theory, he demonstrated that feedback between PAR biochemistry and the actively generated stresses driving cortical flow is sufficient to explain the polarization process. Kun-Chun Lee (University of California, Davis) addressed an important, but understudied, question in cell mechanics: How do cells turn while in motion? Inspired by observations of keratocyte cells, he presented a computational model in which positive mechanical feedback between adhesions stick–slip and effective myosin drift in the moving cell framework and myosin-dependent actin disassembly causes a transient destabilization of myosin and adhesion distributions, allowing the cell to turn. Jonas Dorn (University of Montreal) presented a novel computational model of contractile-ring ingression in cytokinesis. His work explores the striking observation that ring ingression in C. elegans does not occur concentrically; it is usually strongly asymmetric. Using a minimal model and parameters derived from experiments, he showed that ring asymmetry could result from curvature-induced filament alignment. Moreover, the model suggests that nonconcentric ring closure is energetically favorable compared with symmetric ingression. Ewa Paluch (Max Planck Institute of Molecular Cell Biology and Genetics; International Institute of Molecular and Cell Biology) investigated the contribution of contractile forces exerted by the actin cortex at the cell poles to cell shape control during cytokinesis. A study combining theory and quantitative experiments showed that if polar contractile forces exceed a threshold, shape asymmetries can arise in which one pole contracts at the expense of the other. Such asymmetries can lead to shape oscillations and division failure. An analytical, coarse-grained model coupling cortex contractility, cell elasticity, and cortical actin turnover indicates that oscillations are an intrinsic feature of the actin cortex. In cell division, shape asymmetries and oscillations are detrimental, as they compromise the success of cytokinesis. The formation of membrane blebs, commonly observed at the poles of dividing cells, could effectively decrease polar tension and limit the occurrence of instabilities. Finally, Hana El-Samad (University of California, San Francisco) discussed some implications of the ubiquitous stochasticity of cellular networks. Specifically, she presented a systematic dissection of the structure of gene expression noise in the yeast Saccharomyces cerevisiae. Her data suggested the presence of substantial pathway variability shared exclusively across similarly regulated genes, resulting in modular signaling structures spanning distinct functional classes, such as the MSN2/4 stress-response pathway, amino acid biosynthesis, and mitochondrial maintenance. A combination of bioinformatic analyses, computational modeling, and controlled genetic perturbations further confirmed the presence and functional importance of these well-delineated “noise regulons,” and established pathway noise is a quantitative tool for exploring pathway features and regulatory relationships, even in unstimulated systems.
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Oct 10, 2024
Daria A Lachinova + 4
