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SUMMARY:Reverse Engineering the Forces that Drive Embryogenesis - Professo
 r G. Wayne Brodland\,  University of Waterloo
DTSTART:20140530T130000Z
DTEND:20140530T140000Z
UID:TALK52007@talks.cam.ac.uk
CONTACT:Ms Helen Gardner
DESCRIPTION:If we are to fully understand the remarkable processes through
  which organs and other critical structures are formed during embryo devel
 opment\, we must find ways map the mechanical forces that drive them. Typi
 cal in vitro experimental approaches such as AFM\, micropipette aspiration
 \, magnetic cytometry and laser ablation provide information at only a sin
 gle location and time\, and embryo-to-embryo variability precludes the con
 struction of maps from such data.\n\nThe key to making force maps came thr
 ough computational models\, another standard tool for learning about force
 s in embryos. In a traditional model\, the driving forces are specified an
 d a computational engine calculates the motions that they would produce. F
 inding the exact forces needed to produce a particular\, observed pattern 
 of motion could be a long and tedious process\, involving a sequence of pa
 rametric studies. Even so\, this approach gave rise to many successes\, in
 cluding understanding of cell sorting and neurulation\, and it set the sce
 ne for a family of methods that allow forces maps to be built.\n\nIn 2010\
 , the author and his group found a way to invert the matrix equations at t
 he heart of these models so that motions could be specified and driving fo
 rces found. Mathematical challenges related to rank deficiency and conditi
 oning 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 chall
 enges arise when this approach is applied to wound healing and other motio
 ns that occur within the plane of a cell sheet. As we reported in 2014\, t
 hese challenges can be overcome by removing the popular assumption that ce
 ll edges are straight\, and allowing them to be curved. This new approach\
 , called the Cellular Force Inference Tookit (CellFIT) overcomes the drawb
 acks of VFM and other related methods\, and it is general in its applicati
 on. Tests using synthetic data show that the edge-tension and intracellula
 r 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.\n\nWhen ap
 plied to various embryonic epithelia\, the method reveals force and pressu
 re 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 t
 o the point that it is able to reverse engineer the forces that drive embr
 yogenesis.
LOCATION:Oatley Seminar Room\, Department of Engineering
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