Affiliations: Department of Physics, University of Missouri, Columbia, MO 65211, USA | Department of Biophysics and Medical Informatics, Victor Babes University of Medicine and Pharmacy Timisoara, 1900 Timisoara, Romania | Department of Cell Biology and Anatomy, Medical University of South Carolina, SC 29425, USA | Department of Biology, University of Missouri, Columbia, MO 65211, USA
Note: [] Address for correspondence: Gabor Forgacs, Department of Physics, University of Missouri, Columbia, MO 65211, USA. Tel.: +1 573 882 3036; Fax: +1 573 882 4195; E‐mail: forgacsg@missouri.edu.
Abstract: Aggregates of living cells (i.e. model tissue fragments) under appropriate conditions fuse like liquid drops. According to Steinberg's differential adhesion hypothesis (DAH), this may be understood by assuming that cells are motile and tissues made of such cells possess an effective surface tension. Here we show that based on these properties three‐dimensional cellular structures of prescribed shape can be constructed by a novel method: cell aggregate printing. Spherical aggregates of similar size made of cells with known adhesive properties were prepared. Aggregates were embedded into biocompatible gels. When the cellular and gel properties, as well as the symmetry of the initial configuration were appropriately adjusted the contiguous aggregates fused into ring‐like organ structures. To elucidate the driving force and optimal conditions for this pattern formation, Monte Carlo simulations based on a DAH motivated model were performed. The simulations reproduced the experimentally observed cellular arrangements and revealed that the control parameter of pattern evolution is the gel‐tissue interfacial tension, an experimentally accessible parameter.
