MicroMotility: State of the art, recent accomplishments and perspectives on the mathematical modeling of bio-motility at microscopic scales

Mathematical modeling and quantitative study of biological motility (in particular, of motility at microscopic scales) is producing new biophysical insight and is offering opportunities for new discoveries at the level of both fundamental science and technology. These range from the explanation of how complex behavior at the level of a single organism emerges from body architecture, to the understanding of collective phenomena in groups of organisms and tissues, and of how these forms of swarm intelligence can be controlled and harnessed in engineering applications, to the elucidation of processes of fundamental biological relevance at the cellular and sub-cellular level. In this paper, some of the most exciting new developments in the fields of locomotion of unicellular organisms, of soft adhesive locomotion across scales, of the study of pore translocation properties of knotted DNA, of the development of synthetic active solid sheets, of the mechanics of the unjamming transition in dense cell collectives, of the mechanics of cell sheet folding in volvocalean algae, and of the self-propulsion of topological defects in active matter are discussed. For each of these topics, we provide a brief state of the art, an example of recent achievements, and some directions for future research

Cell-center-based model for simulating three-dimensional monolayer tissue deformation

The shape of the epithelial monolayer can be depicted as a curved tissue in three-dimensional (3D) space, where individual cells are tightly adhered to one another. The 3D morphogenesis of these tissues is governed by cell dynamics, and a variety of mathematical modeling and simulation studies have been conducted to investigate this process. One promising approach is the cell-center model, which can account for the discreteness of cells. The cell nucleus, which is considered to correspond to the cell center, can be observed experimentally. However, there has been a shortage of cell-center models specifically tailored for simulating 3D monolayer tissue deformation. In this study, we developed a mathematical model based on the cell-center model to simulate 3D monolayer tissue deformation. Our model was confirmed by simulating the in-plane deformation, out-of-plane deformation, and invagination due to apical constriction

Global morphogenetic flow is accurately predicted by the spatial distribution of myosin motors.

During embryogenesis tissue layers undergo morphogenetic flow rearranging and folding into specific shapes. While developmental biology has identified key genes and local cellular processes, global coordination of tissue remodeling at the organ scale remains unclear. Here, we combine in toto light-sheet microscopy of the Drosophila embryo with quantitative analysis and physical modeling to relate cellular flow with the patterns of force generation during the gastrulation process. We find that the complex spatio-temporal flow pattern can be predicted from the measured meso-scale myosin density and anisotropy using a simple, effective viscous model of the tissue, achieving close to 90% accuracy with one time dependent and two constant parameters. Our analysis uncovers the importance of a) spatial modulation of myosin distribution on the scale of the embryo and b) the non-locality of its effect due to mechanical interaction of cells, demonstrating the need for the global perspective in the study of morphogenetic flow

Collective behavior and self-organization in neural rosette morphogenesis

Neural rosettes develop from the self-organization of differentiating human pluripotent stem cells. This process mimics the emergence of the embryonic central nervous system primordium, i.e., the neural tube, whose formation is under close investigation as errors during such process result in severe diseases like spina bifida and anencephaly. While neural tube formation is recognized as an example of self-organization, we still do not understand the fundamental mechanisms guiding the process. Here, we discuss the different theoretical frameworks that have been proposed to explain self-organization in morphogenesis. We show that an explanation based exclusively on stem cell differentiation cannot describe the emergence of spatial organization, and an explanation based on patterning models cannot explain how different groups of cells can collectively migrate and produce the mechanical transformations required to generate the neural tube. We conclude that neural rosette development is a relevant experimental 2D in-vitro model of morphogenesis because it is a multi-scale self-organization process that involves both cell differentiation and tissue development. Ultimately, to understand rosette formation, we first need to fully understand the complex interplay between growth, migration, cytoarchitecture organization, and cell type evolution

Imaging Approaches and the Quantitative Analysis of Heart Development.

Heart morphogenesis is a complex and dynamic process that has captivated researchers for almost a century. This process involves three main stages, during which the heart undergoes growth and folding on itself to form its common chambered shape. However, imaging heart development presents significant challenges due to the rapid and dynamic changes in heart morphology. Researchers have used different model organisms and developed various imaging techniques to obtain high-resolution images of heart development. Advanced imaging techniques have allowed the integration of multiscale live imaging approaches with genetic labeling, enabling the quantitative analysis of cardiac morphogenesis. Here, we discuss the various imaging techniques used to obtain high-resolution images of whole-heart development. We also review the mathematical approaches used to quantify cardiac morphogenesis from 3D and 3D+time images and to model its dynamics at the tissue and cellular levels.Grant support PGC2018-096486-B-I00 from the Spanish Ministerio de Ciencia e Innovación and Grant H2020-MSCA-ITN-2016-722427 from the EU Horizon 2020 program to M.T. M.S. was supported by a La Caixa Foudation PhD fellowship (LCF/BQ/DE18/11670014) and The Company of Biologists travelling fellowship (DEVTF181145). The CNIC is supported by the Spanish Ministery of Science and the ProCNIC Foundation.S

Regulation of heart development by the planar cell polarity pathway through the actomyosin complex and the mechanical forces

The heart is the first functional organ to form during vertebrate development and it is evolutionarily conserved across species. It is crucial for the proper delivering of essential nutrients and oxygen throughout the embryo's body. Its development is complex and requires fine-tuning processes at levels involving growth, differentiation, and morphogenesis. First, a linear heart tube is formed, followed by cardiac looping, chamber formation, and maturation. As for many organs, the heart arises from a simple epithelium with planar polarity properties. The genetic and molecular programs involved in heart formation have been studied for a long time. However, besides the genetic and cellular contributions to heart formation, little is known about the molecular and cellular components involved in generating tissue and tension forces required in heart morphogenesis. Embryonic heart tube remodeling requires coordination of actomyosin-dependent tissue forces fundamental to the emergence of cardiac chambers and looped heart. It has been established that cardiac chamber remodeling is coordinated through tissue-scale polarization of actomyosin. Here, using zebrafish as a model, I describe the role of actomyosin in generating and distributing the tension forces necessary across the ventricular myocardium during cardiac looping and chamber formation. I describe the spatiotemporal distribution of phosphorylated myosin during embryonic heart formation. A mathematical model was generated to demonstrate that the tissue-scale supracellular polarization of actomyosin within the myocardial epithelium is essential for heart formation. The mathematical model serves as a predictive tool of cardiac looping and chamber formation and supports its dependence on the proper actomyosin distribution. Examining the molecular mechanisms governing the actomyosin activity along the heart tube, I demonstrate that both Rho-associated Protein Kinase 2a (Rock2a) and cardiac-specific Myosin Light Chain Kinase 3 (Mylk3) regulate the actomyosin-based tissue forces through the phosphorylation state of the Myosin Regulatory Light Chain (MRLC). I show that the preferential basal activity of Mylk3 and the apical activity of Rock2a mediate the proper levels of phosphorylated myosin (pMyo) and its polarized distribution along the apicobasal axis within the myocardium. I propose that the antagonistic force-generating activities of Mylk3 and Rock2a facilitate mechano-molecular control of heart tube morphogenesis. Moreover, I show Mylk3 and Rock2a are under the genetic control of Planar Cell Polarity signaling, identifying Mylk3 as a novel tissue-specific effector, downstream of the Vangl2 branch of this signaling pathway. Altogether, these findings describe for the first time a mechano-molecular mechanism necessary for proper looping and chamber formation during heart development

Hydra morphogenesis as phase-transition dynamics

We utilize whole-body Hydra regeneration from a small tissue segment to develop a physics framework for animal morphogenesis. Introducing experimental controls over this process, an external electric field and a drug that blocks gap junctions, allows us to characterize the essential step in the morphological transition - from a spherical shape to an elongated spheroid. We find that spatial fluctuations of the Ca2+ distribution in the Hydra's tissue drive this transition and construct a field-theoretic model that explains the morphological transition as a first-order-like phase transition resulting from the coupling of the Ca2+ field and the tissue's local curvature. Various predictions of this model are verified experimentally.Comment: 8 pages, 4 figures, Supplementary Materia

BMP/Dpp signaling and epithelial morphogenesis in Drosophila development

In this thesis, I mainly investigate how BMP/Dpp signaling is involved in development of the early pupal wing of Drosophila, and the mechanisms coupling Dpp signaling with morphogenesis.Tässä työssä tutkitaan lähinnä sitä, miten BMP / Dpp-signalointi on mukana Drosophilan varhaisen pupalin siiven kehityksessä ja mekanismeja, jotka kytkeytyvät Dpp-signalointiin morfogeneesi kanssa