Lance A. Davidson, PhD

Professor, Wellington C. Carl Faculty Fellow Professor in Developmental Biology Professor in Computational and Systems Biology

Director, Mechanics of Morphogenesis Laboratory

5059 Bioscience Tower 3 | 3501 Fifth Avenue | Pittsburgh, PA 15261 P: 412-383-5820 C: 412-352-8505

lance.a.davidson@pitt.edu

Mechanics of Morphogenesis

Our group has two long-term objectives: (1) to understand the mechanical processes that control morphogenesis, and (2) to apply principles of morphogenesis as a technology to advance cell and tissue engineering. Morphogenesis is the central process of tissue self-assembly that couples physical processes that move cells and tissues with the biological processes that give cells their identity, establish tissue architecture and physiological function. By necessity our research lies at the interface between cell biology, mathematics, physics, and engineering. Projects typicaly involve overlapping expertise that combine cell biological, biophysical, and bioengineering methods.

The Biomechanics of Tissue Elongation

The elongation of the vertebrate body, from head to tail, during early development and the elongation of structures such as long bones during growth are driven by collective cell rearrangement of mesenchymal cells. Our research has uncovered hidden mechanical phenotypes where losses in force production can be compensated by reduced mechanical resistance. Genetic and cell signaling control actomyosin complexes responsible for the mechanics of early embryonic tissues but their spatial organization is regulated by cell geometry and architectural features of the embryo. Our studies in this area require development of microscale mechanical testing, high resolution confocal imaging, and theoretical and computational modeling. Discoveries from this project have provided novel insights into integration of genetic and mechanical programs of development and how these systems are robust against the variation in their environment.

Cardiac Progenitors Sense Mechanical Cues as they Assemble the Heart

The heart is assembled from cells that migrate halfway across the early embryo. As these cells migrate they take instruction from their surroundings, either through chemical signaling or through mechanical cues. These cues drive cells to transition from one type to another. Recently, we have found a fundamental transition, that converts cells from a loose mass to a structured sheet, requires cells sense their mechanical environment. An altered environment, leading to delayed or precocious transitions during these early stages, produce commonly seen structural defects analogous to those seen in human congenital heart defects.

Advancing Cell and Tissue Engineering

In these projects we seek to actuate morphogenetic programs within engineered microenvironments to achieve specific end-points. For instance, using 3D microfabricated structures to direct either single cell or collective migration within tissues. We utilize additive and subtractive manufacturing and scaffold-free engineering to enhance ‘organs-in-a-dish’ and ‘organs-on-a-dish’ applications. We develop microfluidic tools in order to control the local biochemical microenvironment enabling high spatial and temporal resolution actuation to be combined with rapid non-invasive interrogation by live-cell reporters.