Mechanics of Morphogenesis:
The Biology and Engineering Behind the Mysteries of Embryonic Development.

Physics Matters! Biological processes play out in the physical world where work, energy, and kinetics dictate the shape and form of embryos and organs.

Our mission is two-fold, first, to expose the ways in which the environment, genome, cell biology, and mechanics are integrated during development, and second, to turn the principles of development into practical technologies for tissue engineering.

Elucidating the direct role of mechanics in morphogenesis.
How the embryo and its component organ systems form is a central mystery in biology. Sequencing and molecular genetics have revealed remarkable homologies in the genes and proteins that coordinate these processes. Many animals share common cell signaling pathways and gene regulatory networks, yet, the physical mechanisms that are responsible for converting genetic information into diverse functioning structures have been elusive. Our research program has pioneered the field of developmental biomechanics and is now showing how genetics connects to the physical forces and processes that drive shape change in embryos. This work began with Davidson’s PhD work on sea urchin gastrulation and continues today.

Identifying molecular mechanisms and cell behaviors responsible for tissue-scale morphogenesis.
Key connections between genes and the physical mechanics that shape tissues can be observed at the cellular level. Studies of cell behavior and collective cell movements in the embryo, e.g. morphogenesis, shed light on the ways proteins work to establish mechanical processes. The MechMorpho group's work on morphogenesis in the embryo has exposed connections between signaling systems such as the planar cell polarity pathway and mechanically active cellular processes. Our work has described novel movements and biological processes and have shown how cell behaviors are not merely the output of "gene-arrow-gene" networks but rather systems that coordinate multiple physical and molecular processes within a tissue.

Computational models of cell and developmental biology.
Lance moved from industry to a PhD program in Biophysics with the goal of developing advanced computational models in cell and developmental biology. Due to the foundational lack of physical measurements on embryos, this effort naturally morphed into one that currently combines theoretical with experimental biomechanics and biophysics. The MechMorpho/Davidson group and collaborators continues development of computational models that focus on closing the gap between current biochemical knowledge of cytoskeleton (F-actin and keratin intermediate filaments) and adhesion, and areas of biomechanics and mechanobiology. In recent work we have been integrating these efforts with machine learning and systems bioengineering tools.


The role of extracellular matrix (ECM) in developing vertebrate embryos.
ECM has long fascinated developmental biologists. ECM, especially fibronectin and laminin are ubiquitously expressed in early vertebrate and mammalian embryos. Knockout studies against ECM and their cellular receptors, as well as knock-down and dominant negative studies support the critical roles of ECM in both establishing cell identities and organizing laminar germ layers in the early embryo. Furthermore, ECM also plays a key role in the mechanical self-assembly of the embryo. Lance’s postdoc work in the frog Xenopus laevis described the spatial and temporal assembly of fibronectin matrix and tested the role of fibronectin and its cellular receptors in collective cell migration. Continuing work in the group investigate the role of ECM in tissue-scale biomechanics and collective cell movements in the early embryos.

Education: Embryological approaches to morphogenesis using Xenopus.
Xenopus laevis, as a model amphibian developmental model, offers unparalleled access to the processes that drive morphogenesis. External fertilization, large size, fast development, and ease of husbandry and rearing continue to make this a excellent model for learning basic principles of experimental embryology. The large size and synchronous development makes Xenopus a unique source of material for biochemistry and bioinformatics. The ability to microsurgically dissect the embryo and the robust development of organotypic isolates isolates offers unparalleled opportunities to study the physical mechanics of vertebrate development. Xenopus continues to make valuable contributions to basic science and continues to drive translational research from those discoveries.

Applying the principles of developmental biology to engineer tissues.
Arthur C Clarke postulated that “any sufficiently advanced technology is indistinguishable from magic.” We are struck by the complexity and robustness of embryonic development and seek to turn knowledge of developmental biology into a formal engineering discipline. We have developed a series of collaborations to test and highlight design principles for tissue engineers. In these collaborations we have applied microfluidics and microfabrication techniques to control complex programs of morphogenesis. The ability to forward engineer tissue self-assembly is critical to unlock the translational potential of developmental biology.