Lauffenburger:Cell Substratum Adhesion, Signaling, and Migration

Lauffenburger Lab

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Cell Substratum Adhesion, Signaling, and Migration Our objective here is to provide fundamental information on the relationship between adhesion molecule properties and aspects of dynamic adhesion of cells on ligand-coated biomaterials. Emphasis can range from physicochemical aspects of adhesion, to structural aspects of the materials substratum, to biological signaling processes stimulated by adhesion. A major area of work is relating both adhesion-based signaling and soluble growth factor-based signaling to the biophysical processes governing cell migration. This cell behavior function is crucial to therapies for inflammation, cancer, and wound healing as well as applications in tissue engineering. Hyung-Do Kim (BE doctoral), in collaboration with Prof. Paul Matsudaira (BE, Biology and Whitehead Institute for Biomedical Research, MIT) and Prof. Frank Gertler (Biology, MIT) Quantitative analysis of EGFR signaling-mediated tumor cell migration in three-dimensional matrices. Development of data-driven cue-signal-response models to characterize the role of EGFR and protease signaling in 3D motility biophysics and cell-matrix interactions. Development of experimental platforms using current imaging techniques for quantitative studies of cell migration. Shelly Peyton (BE postdoctoral, joint with Dr. Linda Griffith) Adult Stem Cell Migration Behavior in 3D Synthetic ECMs Currently, a large amount of effort is being put forth on combining marrow progenitor cells, or mesenchymal stem cells (MSCs) with 3D scaffolds to direct bone regeneration in critical size bone defects. Consequently, many people are investigating how the bio-physical and –chemical properties of 3D scaffolds can facilitate MSC survival, proliferation, and differentiation into appropriate lineages. However, little is known about how implanted MSCs migrate through these scaffolds. I am currently using a synthetic PEG-based system in which adhesivity, matrix stiffness, and porosity can be independently tuned. We are using this highly tunable system to analyze distinct biophysical features of 3D scaffolds on MSC migration. Combined with existing data on MSC proliferation, survival, and differentiation in 3D scaffolds by our lab and others, this information on MSC motility could be very powerful for future intelligent scaffold design for MSC-directed bone regeneration in vivo. Tharathorn (Joy) Rimchala (BE Doctoral), in collaboration with Prof. Roger Kamm (MechE/BE, MIT) Intracellular Signaling measurement and cell decision model in endothelial angiogenesis