Biology subjects

Ito, A. M.

Publications and source records attributed to Ito, A. M..

3 recordsLinked to original sources

bioRxiv2024

Cell position-based evaluation of mechanical features of cells in multicellular systems

Measurement of mechanical forces of cell-cell interactions is important for studying the emergence of diverse three-dimensional morphologies of multicellular organisms. We previously reported an image-based statistical method for inferring effective pairwise forces of cell-cell interactions (i.e., attractive/repulsive forces), where a cell particle model was fitted to cell tracking data acquired by live imaging. However, because the particle model is a coarse-grained model, it remains unclear how the pairwise forces relates to sub-cellular mechanical components including cell-cell adhesive forces. Here we applied our inference method to cell tracking data generated by vertex models that assumed sub-cellular components. Through this approach, we investigated the relationship between the effective pairwise forces and various sub-cellular components: cell-cell adhesion forces, cell surface tensions, cell-extracellular matrix (ECM) adhesion, traction forces between cells and ECM, cell growth, etc. We found that the cell-cell adhesion forces were attractive, and both the cell surface tensions and cell-ECM adhesive forces were repulsive, etc. These results indicate that sub-cellular mechanical components can contribute to the effective attractive/repulsive forces of cell-cell interactions. This comprehensive analysis provides theoretical bases for linking the pairwise forces to the sub-cellular mechanical components: this showcase is useful for speculating the sub-cellular mechanical components from the information of cell positions, and for interpreting simulation results based on particle models.

biophysics↗

bioRxiv2023

Effective mechanical potential of cell-cell interaction in tissues harboring cavity and in cell sheet toward morphogenesis

Measuring mechanical forces of cell-cell interactions is important for studying morphogenesis in multicellular organisms. We previously reported an image-based statistical method for inferring effective mechanical potentials of pairwise cell-cell interactions by fitting cell tracking data with a theoretical model. However, whether this method is applicable to tissues with non-cellular components such as cavities remains elusive. Here we evaluated the applicability of the method to cavity-harboring tissues. Using synthetic data generated by simulations, we found that the effect of expanding cavities was added to the pregiven potentials used in the simulations, resulting in the inferred effective potentials having an additional repulsive component derived from the expanding cavities. Interestingly, simulations by using the effective potentials reproduced the cavity-harboring structures. Then, we applied our method to the mouse blastocysts, and found that the inferred effective potentials can reproduce the cavity-harboring structures. Pairwise potentials with additional repulsive components were also detected in two-dimensional cell sheets, by which curved sheets including tubes and cups were simulated. We conclude that our inference method is applicable to tissues harboring cavities and cell sheets, and the resultant effective potentials are useful to simulate the morphologies.

biophysics↗

bioRxiv2019

Effective physical properties of cell-cell interaction explain basic structural units of three-dimensional morphogenesis

Mechanical forces are critical for the emergence of diverse three-dimensional morphologies of multicellular systems. However, it remains unclear what kind of mechanical parameters at cellular level substantially contribute to tissue morphologies. This is largely due to technical limitations of live measurements of cellular forces. Here we developed a framework for inferring and modeling mechanical forces of cell-cell interactions. First, by analogy to coarse-grained models in molecular and colloidal sciences, we approximated cells as particles, where mean forces (i.e. effective forces) of pairwise cell-cell interactions are considered. Then, the forces were statistically inferred by fitting the mathematical model to cell tracking data. This method was validated by using synthetic cell tracking data resembling various in vivo situations. Application of our method to the cells in the early embryos of mice and the nematode Caenorhabditis elegans revealed that cell-cell interaction forces can be written as a pairwise potential energy in a manner dependent on cell-cell distances. Importantly, the profiles of the pairwise potentials were quantitatively different among species and embryonic stages, and the quantitative differences correctly described the differences of their morphological features such as spherical vs. distorted cell aggregates, and tightly vs. non-tightly assembled aggregates. We conclude that the effective pairwise potential of cell-cell interactions is a live measurable parameter whose quantitative differences can be a parameter describing three-dimensional tissue morphologies. Author summaryEmergence of diverse three-dimensional morphologies of multicellular organisms is one of the most intriguing phenomena in nature. Due to the complex situations in living systems (e.g. a lot of genes are involved in morphogenesis.), a model for describing the emergent properties of multicellular systems has not been established. To approach this issue, approximation of the complex situations to limited numbers of parameters is required. Here, we searched for mechanical parameters for describing morphologies. We developed a statistical method for inferring mechanical potential energy of cell-cell interactions in three-dimensional tissues; the mechanical potential is an approximation of various mechanical components such as cell-cell adhesive forces, cell surface tensions, etc. Then, we showed that the quantitative differences in the potential is sufficient to reproduce basic three-dimensional morphologies observed during the mouse and C. elegans early embryogenesis, revealing a direct link between cellular level mechanical parameters and three-dimensional morphologies. Our framework provides a noninvasive tool for measuring spatiotemporal cellular forces, which would be useful for studying morphogenesis of larger tissues including organs and their regenerative therapy.

biophysics↗