Groups of mesenchymal cells dispersed in a loose and fibruous ECM compact to form condensates. We use this fundamental cell behavior to engineer tissues that fold up along specific trajectories, in a manner analagous to self-folding origami.
We describe a technology that enables deterministic printing of tailored groups of cells and reagents to arrays exceeding 10,000 features. In this image we printed exactly one green cell and one red cell to each feature in an array.
We describe monovalent nanoparticles that can be used to independently localize or deliver quantitative mechanical loads to single cell surface receptors.
Three-dimensional image of a tissue constructed using DNA-programmed assembly of cells (DPAC). We aimed to synthesize a tissue with a structure similar to the Terminal Ductal Lobular Unit (TDLU) of the breast.
We investigate how the mammary gland maintains a single three-dimensional structure through a robust program of self-organization. In the movie, luminal (green) and myoepithelial (red) cells self-organize correctly in extracellular matrix (left), but into an inverted structure in non-adhesive microenvironments such as agarose (right).
A simple method for generating site-specific DNA-protein conjugates is presented. This method provides a means of assembling antibody fragments on DNA scaffolds in precisely defined nanoscale geometries. These constructs will find utility as nanoscale probes of receptor organization at the cell surface.
Controlling the valency of targeting elements on nanoparticles is a major challenge. Here we describe a modular and scalable synthetic strategy to generate monovalent semiconductor quantum dots by steric exclusion. Phosphorothioate DNA is mixed with ZnS coated CdSe QDs to produce targetable and highly fluorescent nanoparticles of a single valency.
Variability in cell state can arise as a consequence of noisy gene expression, microenvironmental heterogeneity, or somatic mutations. Heterogeneity can become accentuated in tumors. In this paper, we find that tissues exhibiting heterogeneity in signaling through the Ras oncogene can drive the emergence of more invasive collective cell behaviors when compared to tissue with more homogeneous signaling through Ras.
Read a review of this work in MIT's Technology Review. This work was also featured in a C&E news Science and Technology Concentrates and in the August 2009 issue of the HHMI Bulletin.
IL-3 producing cells (green, top), but not controls (green, bottom) rescue the growth of IL-3 dependent hematopoietic progenitors (Phase). This paracrine signaling network mimics certain aspects of immune system function.
A library of macrocyclic peptide fumaramides.