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Mollusk shells are an ideal model system for understanding the morpho-elastic basis of morphological evolution of invertebrates’ exoskeletons. During the formation of the shell, the mantle tissue secretes proteins and minerals that calcify to form a new incremental layer of the exoskeleton. Most of the existing literature on the morphology of mollusks is descriptive. The mathematical understanding of the underlying coupling between pre-existing shell morphology, de novo surface deposition and morpho-elastic volume growth is at a nascent stage, primarily limited to reduced geometric representations. Here, we propose a general, three-dimensional computational framework coupling pre-existing morphology, incremental surface growth by accretion, and morpho-elastic volume growth. We exercise this framework by applying it to explain the stepwise morphogenesis of seashells during growth: new material surfaces are laid down by accretive growth on the mantle whose form is determined by its morpho-elastic growth. Calcification of the newest surfaces extends the shell as well as creates a new scaffold that constrains the next growth step. We study the effects of surface and volumetric growth rates, and of previously deposited shell geometries on the resulting modes of mantle deformation, and therefore of the developing shell’s morphology. Connections are made to a range of complex shells ornamentations. [ABSTRACT FROM AUTHOR]

It is well established that the mechanical environment influences cell functions in health and disease. Here, we address how the mechanical environment influences tumor growth, in particular, the shape of solid tumors. In an in vitro tumor model, which isolates mechanical interactions between cancer tumor cells and a hydrogel, we find that tumors grow as ellipsoids, resembling the same, oft-reported observation of in vivo tumors. Specifically, an oblate ellipsoidal tumor shape robustly occurs when the tumors grow in hydrogels that are stiffer than the tumors, but when they grow in more compliant hydrogels they remain closer to spherical in shape. Using large scale, nonlinear elasticity computations we show that the oblate ellipsoidal shape minimizes the elastic free energy of the tumor-hydrogel system. Having eliminated a number of other candidate explanations, we hypothesize that minimization of the elastic free energy is the reason for predominance of the experimentally observed ellipsoidal shape. This result may hold significance for explaining the shape progression of early solid tumors in vivo and is an important step in understanding the processes underlying solid tumor growth. [ABSTRACT FROM AUTHOR]

Background: We consider a focal adhesion to be made up of molecular complexes, each consisting of a ligand, an integrin molecule, and associated plaque proteins. Free energy changes drive the binding and unbinding of these complexes and thereby controls the focal adhesion's dynamic modes of growth, treadmilling and resorption. Principal Findings: We have identified a competition among four thermodynamic driving forces for focal adhesion dynamics: (i) the work done during the addition of a single molecular complex of a certain size, (ii) the chemical free energy change associated with the addition of a molecular complex, (iii) the elastic free energy change associated with deformation of focal adhesions and the cell membrane, and (iv) the work done on a molecular conformational change. We have developed a theoretical treatment of focal adhesion dynamics as a nonlinear rate process governed by a classical kinetic model. We also express the rates as being driven by out-of-equilibrium thermodynamic driving forces, and modulated by kinetics. The mechanisms governed by the above four effects allow focal adhesions to exhibit a rich variety of behavior without the need to introduce special constitutive assumptions for their response. For the reaction-limited case growth, treadmilling and resorption are all predicted by a very simple chemo-mechanical model. Treadmilling requires symmetry breaking between the ends of the focal adhesion, and is achieved by driving force (i) above. In contrast, depending on its numerical value (ii) causes symmetric growth, resorption or is neutral, (iii) causes symmetric resorption, and (iv) causes symmetric growth. These findings hold for a range of conditions: temporally-constant force or stress, and for spatiallyuniform and non-uniform stress distribution over the FA. The symmetric growth mode dominates for temporally-constant stress, with a reduced treadmilling regime. Significance: In addition to explaining focal adhesion dynamics, this treatment can be coupled with models of cytoskeleton dynamics and contribute to the understanding of cell motility. [ABSTRACT FROM AUTHOR]

In this work, we describe the CRIMSON (CardiovasculaR Integrated Modelling and SimulatiON) software environment. CRIMSON provides a powerful, customizable and user-friendly system for performing three-dimensional and reduced-order computational haemodynamics studies via a pipeline which involves: 1) segmenting vascular structures from medical images; 2) constructing analytic arterial and venous geometric models; 3) performing finite element mesh generation; 4) designing, and 5) applying boundary conditions; 6) running incompressible Navier-Stokes simulations of blood flow with fluid-structure interaction capabilities; and 7) post-processing and visualizing the results, including velocity, pressure and wall shear stress fields. A key aim of CRIMSON is to create a software environment that makes powerful computational haemodynamics tools accessible to a wide audience, including clinicians and students, both within our research laboratories and throughout the community. The overall philosophy is to leverage best-in-class open source standards for medical image processing, parallel flow computation, geometric solid modelling, data assimilation, and mesh generation. It is actively used by researchers in Europe, North and South America, Asia, and Australia. It has been applied to numerous clinical problems; we illustrate applications of CRIMSON to real-world problems using examples ranging from pre-operative surgical planning to medical device design optimization., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CAF and CA are Members of CRIMSON Technologies LLC, a company established to support the future development of CRIMSON.