Cinemechanometry (CMM): A Method to Determine the Forces that Drive Morphogenetic Movements from Time-Lapse Images
- 217 Downloads
Although cell-level mechanical forces are crucial to tissue self-organization in contexts ranging from embryo development to cancer metastases to regenerative engineering, the absence of methods to map them over time has been a major obstacle to new understanding. Here, we present a technique for constructing detailed, dynamic maps of the forces driving morphogenetic events from time-lapse images. Forces in the cell are considered to be separable into unknown active driving forces and known passive forces, where actomyosin systems and microtubules contribute primarily to the first group and intermediate filaments and cytoplasm to the latter. A finite-element procedure is used to estimate the field of forces that must be applied to the passive components to produce their observed incremental deformations. This field is assumed to be generated by active forces resolved along user-defined line segments whose location, often along cell edges, is informed by the underlying biology. The magnitudes and signs of these forces are determined by a mathematical inverse method. The efficacy of the approach is demonstrated using noisy synthetic data from a cross section of a generic invagination and from a planar aggregate that involves two cell types, edge forces that vary with time and a neighbor change.
KeywordsCinemechanometry (CMM) Video force microscopy Cell mechanics Morphogenetic movements Driving forces Tissue mechanics Computational modeling Finite elements Inverse methods
Funding for this project was provided by the Human Frontiers Science Program (HFSP). The authors thank Shane Hutson and Vito Conte for helpful discussions related to the manuscript.
- 7.Chen, X., and G. W. Brodland. Multi-scale finite element modeling allows the mechanics of amphibian neurulation to be elucidated. Phys. Biol. 5:015003 (15 pp), 2008.Google Scholar
- 11.Davis, T. A. Direct Methods for Sparse Linear Systems. Philadelphia: SIAM, 2006.Google Scholar
- 16.Haykin, S. S. Modern Filters. New York: Macmillan, 1989.Google Scholar
- 17.Hibbeler, R. C. Mechanics of Materials. Englewood Cliffs, NJ: Prentice-Hall, 2005.Google Scholar
- 27.Nash, J. C. Compact Numerical Methods for Computers. Bristol: Adam Hilget Ltd, 1979.Google Scholar