Tissue-Scale Mechanical Coupling Reduces Morphogenetic Noise to Ensure Precision during Epithelial Folding.

Morphological constancy is universal in developing systems. It is unclear whether precise morphogenesis stems from faithful mechanical interpretation of gene expression patterns. We investigate the formation of the cephalic furrow, an epithelial fold that is precisely positioned with a linear morphology. Fold initiation is specified by a precise genetic code with single-cell row resolution. This positional code activates and spatially confines lateral myosin contractility to induce folding. However, 20% of initiating cells are mis-specified because of fluctuating myosin intensities at the cellular level. Nevertheless, the furrow remains linearly aligned. We find that lateral myosin is planar polarized, integrating contractile membrane interfaces into supracellular "ribbons." Local reduction of mechanical coupling at the "ribbons" using optogenetics decreases furrow linearity. Furthermore, 3D vertex modeling indicates that polarized, interconnected contractility confers morphological robustness against noise. Thus, tissue-scale mechanical coupling functions as a denoising mechanism to ensure morphogenetic precision despite noisy decoding of positional information.

Improved in vitro models for preclinical drug and formulation screening focusing on 2D and 3D skin and cornea constructs.

The present overview deals with current approaches for the improvement of in vitro models for preclinical drug and formulation screening which were elaborated in a joint project at the Center of Pharmaceutical Engineering of the TU Braunschweig. Within this project a special focus was laid on the enhancement of skin and cornea models. For this reason, first, a computation-based approach for in silico modeling of dermal cell proliferation and differentiation was developed. The simulation should for example enhance the understanding of the performed 2D in vitro tests on the antiproliferative effect of hyperforin. A second approach aimed at establishing in vivo-like dynamic conditions in in vitro drug absorption studies in contrast to the commonly used static conditions. The reported Dynamic Micro Tissue Engineering System (DynaMiTES) combines the advantages of in vitro cell culture models and microfluidic systems for the emulation of dynamic drug absorption at different physiological barriers and, later, for the investigation of dynamic culture conditions. Finally, cryopreserved shipping was investigated for a human hemicornea construct. As the implementation of a tissue-engineering laboratory is time-consuming and cost-intensive, commercial availability of advanced 3D human tissue is preferred from a variety of companies. However, for shipping purposes cryopreservation is a challenge to maintain the same quality and performance of the tissue in the laboratory of both, the provider and the customer.

On a new model for inhomogeneous volume growth of elastic bodies.

In general, growth characterises the process by which a material increases in size by the addition of mass. In dependence on the prevailing boundary conditions growth occurs in different, often complex ways. However, in this paper we aim to develop a model for biological systems growing in an inhomogeneous manner thereby generating residual stresses even when growth rates and material properties are homogeneous. Consequently, a descriptive example could be a body featuring homogeneous, isotropic material characteristics that grows against a barrier. At the moment when it contacts the barrier inhomogeneous growth takes place. If thereupon the barrier is removed, some types of bodies keep the new shape mainly fixed. As a key idea of the proposed phenomenological approach, we effort the theory of finite plasticity applied to the isochoric part of the Kirchhoff stress tensor as well as an additional condition allowing for plastic changes in the new grown material, only. This allows us to describe elastic bodies with a fluid-like growth characteristic. Prominent examples are tumours where the characteristic macro mechanical growth behaviour can be explained based on cellular arguments. Finally, the proposed framework is embedded into the finite element context which allows us to close this study with representative numerical examples.

Recent advances in mechanical characterisation of biofilm and their significance for material modelling.

In recent years, the advances in microbiology show that biofilms are structurally complex, dynamic and adaptable systems including attributes of multicellular organisms and miscellaneous ecosystems. One may distinguish between beneficial and harmful biofilms appearing in daily life as well as various industrial processes. In order to advance the growth of the former or prevent the latter type of biofilm, a detailed understanding of its properties is indispensable. Besides microbiological aspects, this concerns the determination of mechanical characteristics, which provides the basis for material modelling. In the present paper the existing experimental methods that have been proposed since the 1980s are reviewed and critically discussed with respect to their usefulness and applicability to develop numerical modelling approaches.