Directed Self Assembly of Complex Branching Micro-Tissues

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We've developed a new technology based on micro-molded nonadhesive agarose to guide the self assembly of 3D micro-tissues. Mono-disperse cells are pipetted into the micro-mold, they settle into the molded features, are unable to bind to the nonadhesive agarose and so spontaneously self assembly 3D micro-tissues. By making complex features in the micro-molds, we've shown for the first time that cells will self assembly complex structures such as rods, toroids and honeycombs. Little is understood about the rules that govern this directed cellular self-assembly process, especially for complex branching structures and so the overarching goal of this proposal is to define and quantify these rules. Our hypothesis is that the rules of selfassembly differ between specific cell types and that in addition to surface adhesive forces, cytoskeletal mediated tension/contraction contribute to cell specific differences and significantly influence the directed self assembly of complex micro-tissues. To test this hypothesis and define the rules of directed self assembly, we propose to use five cell lines and their mixtures, normal human fibroblasts (NHF), a hepatocyte cell line (H35), smooth muscle cells (SMC) and two endothelial cell lines; human umbilical cord vein endothelial cells (HUVEC) and calf pulmonary artery endothelial cells (CPAE) to test the following specific aims: Aim 1. To determine cell type differences in directed self assembly and their ability to generate complex shapes. Aim 2. To quantify the respective roles of cytoskeletal mediated contraction and cell surface adhesion proteins on directed self-assembly. Modified