University of Cambridge > Talks.cam > Engineering Department Bio- and Micromechanics Seminars > Reverse Engineering the Forces that Drive Embryogenesis

Reverse Engineering the Forces that Drive Embryogenesis

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If we are to fully understand the remarkable processes through which organs and other critical structures are formed during embryo development, we must find ways map the mechanical forces that drive them. Typical in vitro experimental approaches such as AFM , micropipette aspiration, magnetic cytometry and laser ablation provide information at only a single location and time, and embryo-to-embryo variability precludes the construction of maps from such data.

The key to making force maps came through computational models, another standard tool for learning about forces in embryos. In a traditional model, the driving forces are specified and a computational engine calculates the motions that they would produce. Finding the exact forces needed to produce a particular, observed pattern of motion could be a long and tedious process, involving a sequence of parametric studies. Even so, this approach gave rise to many successes, including understanding of cell sorting and neurulation, and it set the scene for a family of methods that allow forces maps to be built.

In 2010, the author and his group found a way to invert the matrix equations at the heart of these models so that motions could be specified and driving forces found. Mathematical challenges related to rank deficiency and conditioning had to be overcome, but when this new approach, called Video Force Microscopy (VFM), was applied to ventral furrow formation in Drosophila, its maps gave the forces acting along each cell membrane, and with sub-minute temporal resolution. As we and others have found, additional challenges arise when this approach is applied to wound healing and other motions that occur within the plane of a cell sheet. As we reported in 2014, these challenges can be overcome by removing the popular assumption that cell edges are straight, and allowing them to be curved. This new approach, called the Cellular Force Inference Tookit (CellFIT) overcomes the drawbacks of VFM and other related methods, and it is general in its application. Tests using synthetic data show that the edge-tension and intracellular pressure maps it produces typically have errors as small as five percent. The method has good noise rejection properties and its solutions can be assessed using tools such as residuals and covariance matrices.

When applied to various embryonic epithelia, the method reveals force and pressure patterns consistent with experiments and force details and variability levels that are sometimes surprising, but confirmable retrospectively. It can also be applied to tissues that are suitably fixed. These encouraging findings suggest that the field of cellular force inference has matured to the point that it is able to reverse engineer the forces that drive embryogenesis.

This talk is part of the Engineering Department Bio- and Micromechanics Seminars series.

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