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Icosahedral capsids are ubiquitous among spherical viruses, yet their assem- bly pathways and governing interactions remain elusive. We present a molecular dynamics model that incorporates essential physical and biological interactions, including protein diffusion, genome flexibility, and a conformational switch that mimics allostery and activates the elastic properties of proteins upon binding. This switch makes the simulations computationally feasible and enables the assembly of icosahedral capsids around a flexible genome—overcoming long-standing lim- itations in previous models. Using this framework, we successfully reproduce the self-assembly of subunits around a flexible genome into icosahedral shells with numbers greater than one – most notably 3, the most common structure in na- ture – a feat that rigid-body models have so far failed to achieve. We systematically explore the range of morphologies formed with different genome architectures, in line with in vitro experiments using cowpea chlorotic mottle virus capsid proteins: viral RNAs with more complex structure form more complete and stable capsids than linear ones. These results provide a predictive framework for genome-guided assembly and capsid design. 

Understanding the mechanisms of the cellular aging processes is crucial for attempting to extend organismal lifespan and for studying age-related degenerative diseases. Yeast cells divide through budding, providing a classical biological model for studying cellular aging. With their powerful genetics, relatively short cell cycle, and well-established signaling pathways also found in animals, yeast cells offer valuable insights into the aging process. Recent experiments suggested the existence of two aging modes in yeast characterized by nucleolar and mitochondrial declines, respectively. By analyzing experimental data, this study shows that cells evolving into those two aging modes behave differently when they are young. While buds grow linearly in both modes, cells that consistently generate spherical buds throughout their lifespan demonstrate greater efficacy in controlling bud size and growth rate at young ages. A three-dimensional multiscale chemical-mechanical model was developed and used to suggest and test hypothesized impacts of aging on bud morphogenesis. Experimentally calibrated model simulations showed that during the early stage of budding, tubular bud shape in one aging mode could be generated by locally inserting new materials at the bud tip, a process guided by the polarized Cdc42 signal. Furthermore, the aspect ratio of the tubular bud could be stabilized during the late stage as observed in experiments in this work. The model simulation results suggest that the localization of new cell surface material insertion, regulated by chemical signal polarization, could be weakened due to cellular aging in yeast and other cell types, leading to the change and stabilization of the bud aspect ratio. 

This review accompanies the Special Issue on the subject of physical virology, which features work presented at the recent Gordon Research Conference (GRC) on this topic [...] 

Throughout history, coronaviruses have posed challenges to both public health and the global economy; nevertheless, methods to combat them remain rudimentary, primarily due to the absence of experiments to understand the function of various viral components. Among these, membrane (M) proteins are one of the most elusive because of their small size and challenges with expression. Here, we report the development of an expression system to produce tens to hundreds of milligrams of M protein per liter ofEscherichia coliculture. These large yields render many previously inaccessible structural and biophysical experiments feasible. Using cryo–electron microscopy and atomic force microscopy, we image and characterize individual membrane-incorporated M protein dimers and discover membrane thinning in the vicinity, which we validated with molecular dynamics simulations. Our results suggest that the resulting line tension, along with predicted induction of local membrane curvature, could ultimately drive viral assembly and budding. 

We extend a recently proposed kinetic theory of virus capsid assembly based on Model A kinetics and study the dynamics of the interconversion of virus capsids of different sizes triggered by a quench, that is, by sudden changes in the solution conditions. The work is inspired by in vitro experiments on functionalized coat proteins of the plant virus cowpea chlorotic mottle virus, which undergo a reversible transition between two different shell sizes (T = 1 and T = 3) upon changing the acidity and salinity of the solution. We find that the relaxation dynamics are governed by two time scales that, in almost all cases, can be identified as two distinct processes. Initially, the monomers and one of the two types of capsids respond to the quench. Subsequently, the monomer concentration remains essentially constant, and the conversion between the two capsid species completes. In the intermediate stages, a long-lived metastable steady state may present itself, where the thermodynamically less stable species predominate. We conclude that a Model A based relaxational model can reasonably describe the early and intermediate stages of the conversion experiments. However, it fails to provide a good representation of the time evolution of the state of assembly of the coat proteins in the very late stages of equilibration when one of the two species disappears from the solution. It appears that explicitly incorporating the nucleation barriers to assembly and disassembly is crucial for an accurate description of the experimental findings, at least under conditions where these barriers are sufficiently large. 

Abstract The exact mechanism controlling cell growth remains a grand challenge in developmental biology and regenerative medicine. The Drosophila wing disc tissue serves as an ideal biological model to study mechanisms involved in growth regulation. Most existing computational models for studying tissue growth focus specifically on either chemical signals or mechanical forces. Here we developed a multiscale chemical-mechanical model to investigate the growth regulation mechanism based on the dynamics of a morphogen gradient. By comparing the spatial distribution of dividing cells and the overall tissue shape obtained in model simulations with experimental data of the wing disc, it is shown that the size of the domain of the Dpp morphogen is critical in determining tissue size and shape. A larger tissue size with a faster growth rate and more symmetric shape can be achieved if the Dpp gradient spreads in a larger domain. Together with Dpp absorbance at the peripheral zone, the feedback regulation that downregulates Dpp receptors on the cell membrane allows for further spreading of the morphogen away from its source region, resulting in prolonged tissue growth at a more spatially homogeneous growth rate.